Guinea-pig platelets contain adherence-inhibiting factor (AIF) in the granule and cytosol fractions. In this study, subgranular localization and properties of granular AIF were examined.
Two AIF molecules, designated AIF-I (about void volume of the column) and AIF-II (about 12 kDa), were eluted, when platelet-granule fraction was subjected to a superose 12 gel chromatography. The neutrophil adherence-inhibiting activity of AIF-I was about fivefold higher than that of AIF-II . AIF-I was sensitive to diisopropylfluoro-phosphate (DFP) and localized in lysosomes, whereas AIF-II was insensitive to DFP and localized in α-granules. Both AIF-I and AIF-II inhibited neutrophil adherence to glass and polystyrene surfaces, but did not inhibit neutrophil adherence to fibronectin-coated polystyrene surface. AIF-II hardly affected neutrophil adherence to type IV collagen-coated polystyrene surface. In contrast, AIF-I significantly inhibited type IV collagen mediated neutrophil adherence.
These results suggest that AIF-II only inhibits neutrophil adherence via nonspecific adsorption sites, whereas AIF-I inhibits neutrophil adherence both via nonspecific adsorption sites and type IV collagen receptors.

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Pulmonary intravascular macrophages reside in the alveolar capillaries of sheep lung. We tested the effects of pulmonary intravascular mcrophages activation on pulmonary microvascular permeability.
Sheep were divided into 3 groups; latex group, indomethacin group and OKY-046 (thromboxane A2 synthetase inhibitor) group. In each group, we infused latex beads emulsion, 1 μm in diameter, 5.46×10¹⁰ beads/kg, intraarterially. In latex group, lymph protein clearance increased significantly during and after the infusion period. In indomethacin group, increases in lymph protein clearance were blocked completely. However, in OKY-046 group, lymph protein clearance increased significantly 3 hours after the infusion period. In each group, peripheral white blood cell counts decreased significantly during the infusion period, and recovered to the baseline valeus after the infusion. Many latex beads were caught by pulmonary intrvascular macrophages selectively.
These results suggest that pulmonary intravascular macrophages activation through their phagocytic uptake of microparticles is essential to increase in pulmonary microvascular permeability in sheep.

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To determine the mechanism by which substance P (SP) activates human neutrophils, we examined the potency of SP for inducing chemotaxis, lysozyme release, and increase in cytosolic free Ca²⁺ concentration ( [Ca²⁺] i) in human blood neutrohils. We also examined the effects of EGTA and of a formyl-Met-Leu-Phe (FMLP) antagonist on the responses. SP (10^-6 to 10^-4 M) induced chemotaxis, lysozyme release, and the increase in [Ca²⁺] i of the neutrophils dose-dependently. Preincubation with EGTA (10 mM) decreased the SP-induced increase in [Ca²⁺] i by 90%, whereas EGTA decreased the FMLP-induced increase in [Ca²⁺] i only by 37%, suggesting that the activations of human neutrophils by SP are dependent on the influx of extracellular Ca²⁺. An FMLP antagonist, boc-Phe-Leu-Phe-Leu-Phe, inhibited the FMLP-induced chemotaxis and increase in [Ca²⁺] i, but it did not inhibit the SP-induced respones.
We suggest that SP induces the activations of human neutrophils by the different mechanism from that of FMLP.

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Skin darkening after cutaneous inflammation is a well known phenomenon but its mechanisms for this hyperpigmentation have not been clarified yet. Because in inflamed skin various mediators such as arachidonic acid metabolites and histamine are found in increased amounts, we have studied their effects on cultured normal human melanocytes. As reported previously we have found that prostaglandine E₂ stimulated normal human melanocytes. In addition histamine, platelet activating factor, bradykinin and arachidonic acid metabolites such as leukotriene (LT) C₄ and LTD₄ also stimulated melanocytes.
They were found to increase the total amounts of immunoreactive tyrosinase and tyrosinase related protein, the number of dendrites and the size of melanocytes. In these proinflammatory mediators, LTC₄ and histamine showed far strong stimulatory effect. On the other hand, serotonin, heparin and other arachidonic acid metabolites such as PGE₁ PGFs and 12-hydroxy eicosatetraenoic acid (12-HETE) did not show any significant stimulatory effect.
Present studies suggest that various proinflammatory chemical mediators, especially LTC₄ and histamine are involved in the stimulation of melanocytes to accelerate the production of melanine and its active transfer to neighboring keratinocytes, resulting into the formation of hyperpigmentation after skin inflammation.

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Rabbit articular chondrocytes produced urokinase-type plasminogen activator (u-PA) into culture supernatants. Human tumor necrosis factor α (TNF) increased the u-PA activity of chondrocyte culture supernatant, in contrast, human interleukin 1α (IL-1) decreased the u-PA activity. U-PA specific inhibitor activity was detected in the culture supernatant using immunocapture method. TNF had no obvious effect on the u-PA inhibitor activity, however IL-1 increased the u-PA inhibitor activity.
The decrease of u-PA activity of chondrocyte culture supernatant appeared to reflect the increase of u-PA inhibitor in the culture supernatant. Inhibition of urokinase by the chondrocyte u-PA inhibitor was observed accompanying with higher molecular weight complex formation, in SDS-polyacrylamide gel electrophoresis followed by fibrin overlay.
TNF may have a more important role in the enzymic degradation mechanism of rabbit articular cartilage than IL-1, since u-PA is one of the potent proteinases responsible for cartilage extracellular matrix degradation.

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We provide evidence that an implanted stratum corneum (SC) fragment induces a distinctive neutrophil infiltration, and that SC activates complement through the alternative pathway to generate C5a anaphylatoxin.
The orthokeratotic SC homogenates were found immuno-electrophoretically to induce the conversion of native C3 to C3b in fresh human serum when the classical pathway was blocked by calcium-chelation. Enzyme immunoassay showed that factor B split product, Bb, was generated by the SC homogenates in the calcium-chelated serum (CaCS) . Radioimmunoassay for C5a also demonstrated that the SC homogenates could generate C5a anaphylatoxin in serum to an extent similar to that in non-treated serum when restricted to the alternative pathway activation. Neutrophil chemotactic activity was generated in CaCS at levels comparable to that generated in non-treated fresh serum. This activity resided in heat-stable substances of corneocytes.
These studies suggest that when the SC comes in contact with serum, it activates complement mainly through the alternative pathway to induce chemotactic C5a anaphylatoxin. Hence, inflammation in normal individuals after a traumatic injury to the skin or rupture of acne comedones, or epidermal cysts and possibly the formation of subcorneal sterlile pustules noted in several dermatoses are explainable through this mechanism.

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In order to investigate the myocardial damage in Kawasaki disease (KD), we determined light chains of human cardiac myosin in the blood by the dot-blotting method and the ELISA method, using the monoclonal antibodies specific for light chains of human cardiac myosin.
In the acute phase of patients with KD, levels of myosin light chains in the blood were approximately 4 to 8 times higher than normal controls in the dot-blotting method. This change was found in about 30% of patients. In the ELISA method, patients with high levels of myosin light chains (over 1 ng/ml) were about 15%.
In the chronic phase about 80% of the patients with high levels returned to normal control level, but about 20% of them were still high levels as compared with normal controls in the dot-blotting method. In the ELISA method, about 80% of the patients with high levels returned to normal control level, but the remaining patients were still detectable.
These results suggest that some patients with KD show the long-term release of myosin light chains resulted from the damage of heart muscle and/or skeletal muscle.
We conclude that the long term evaluation of myocardial damage should be necessary in the patients with KD.

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(1) As a part of the PMS for a marketed drug, data on 35, 653 cases treated with Voltaren^® tablets were collected from 3, 965 medical institutions nation-wide during the 6 years after its market introduction in 1974, and it's efficacy, safety and prescribed indications in daily practice were reassessed.
(2) The most frequent indication for the use of Voltaren^® tablets was in the treatment of diseases of the musculo-skeletal system such as rheumatoid arthritis which comprised about half of all cases. Its use in such disase was prescribed widely by the clinical departments of each medical facility studied and its therapeutic utilization was within the approved indications in 75% of all cases. There was a slightly larger number of females than males and adults aged from 16 to 64 years comprised 83% of all patients which included 15% of elderly patients aged more than 65, and about 82% of these cases received a daily dosage of 75 mg (3 tablets) .
The duration of treatment was one month or less in 82% of all cases that was one week or less for many acute diseases and more than one year for some chronic ailments. With regard to the severity of disease, 83% of the cases were classified as mild or moderate in severity before treatment.
(3) Voltaren^®'s clinical efficacy rate (marked improvement or better) was shown to be 62 to 76% in diseases of the musculo-skeletal system with the exception of rheumatoid arthritis in which the clinical efficacy rate was 46%. In post-operative pain and inflammation Voltaren^®'s clinical efficacy rate was 82 to 88% and 78 to 92% in diseases such as pelvic inflammation, dysmenorrhea, obstetric after-pains, cystitis, inflammation in the anterior chamber of the eyes, pharyngolaryngitis and the common cold syndrome. Voltaren^® achieved a higher efficacy rate in patients whose diseases had only been present for a short time. Good symptomatic improvement rates were obtained in cases of both pain and inflammation.
(4) The incidence of adverse reactions was 7.71%, those of the digestive system being predominant at 86% of the total, followed by such adverse reactions as edema, skin eruptions and nervous/psychiatric symptoms. Most adverse reactions occured within one week of the commencement of treatment and the majority were classified as mild or moderate in degree. As consequence of adverse reactions, Voltaren^® therapy was discontinued in 44% (1, 207/2, 749) of the total number of adverse reactions and this was consisted of 3.4% of all cases (35, 653 cases) . Several cases were classified as severe or relevant such as gastric ulceration or gastrointestinal bleeding (5), jaundice (2), anuria (3), etc. According to an analysis of background factors the incidence of adverse reactions was significantly higher in the case of females, elderly patients, concomitant therapy with other non-steroidal antiinflammtory drugs, with steroids, and in those patients with chronic diseases.

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