Platelet-Activating Factor in the Inflammatory Exudate in the Anaphylactic Phase of Allergic Inflammation in Rats

Int Arch Allergy Immunol

Sugidachi²,

Omata³

et al. 1990

Self Cite

Allergic inflammation was induced by injecting an antigen solution into an air pouch made on the dorsum of immunized rats with the antigen azobenzene-arsonate-conjugated acetyl bovine serum albumin. In this model, leukocyte infiltration into the pouch fluid was prominent 4–8 h after the antigen challenge. Most of the infiltrated leukocytes were neutrophils. Administration of the platelet-activating factor (PAF) antagonists such as CV-3988 and L-652,731 into the air pouch 15 min before and at the time of the antigen challenge failed to suppress leukocyte infiltration at 8 h. However, when the PAF antagonist was injected into an air pouch 4 h after the antigen challenge, neutrophil infiltration at 8 h was suppressed in a dose-dependent manner. Combined treatment with the 5-lipoxygenase inhibitor AA861 and the PAF antagonist did not potentiate the effect of the PAF antagonist, suggesting that participation of leukotriene B₄ in neutrophil infiltration in this model is negligible. Eosinophil infiltration was very weak at 8 h, and the PAF antagonist showed no significant effect. At 8 h, the PAF level in the serum of the immunized rats was significantly higher than that of the nonimmunized rats. Intravenous administration of the PAF antagonist 15 min before the antigen challenge suppressed leukocyte infiltration more effectively than local administration into the pouch. These results indicate that PAF plays a significant role in neutrophil infiltration in allergic inflammation.

Section: Introductionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Possible Role for Platelet-Activating Factor in Neutrophil Infiltration in Allergic Inflammation in Rats

Int Arch Allergy Immunol

Sugidachi²,

Omata³

et al. 1990

Self Cite

“…Since our previous work and the present work demonstrated that treatment with PAF antagonists suppresses neutrophil infiltration into the pouch fluid in the allergic inflammation, it was possible that PAF produced in the inflammatory locus might stimulate leucocytes to produce neutrophil chemotactic factors. PAF levels in the pouch fluid collected 4h after the antigen challenge in the immunized rats, however, were less than the amount detectable by aggregation of guinea-pig platelets (Watanabe et al, 1987;. This result need not imply that PAF is not synthesized at the inflammatory locus, since PAF is easily metabolized into lyso-PAF in the pouch fluid (Watanabe et al, 1987).…”

Section: Discussionmentioning

confidence: 84%

Pharmacological analysis of neutrophil chemotactic factor production by leucocytes and roles of PAF in allergic inflammation in rats

Arakida

Tanabe

et al. 1994

British J Pharmacology

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1 The role of platelet activating factor (PAF) in neutrophil infiltration in air pouch type allergic inflammation in rats was investigated. 2 Neutrophil infiltration into the pouch fluid 8 h after injection of the antigen (azobenzenearsonateconjugated acetyl bovine serum albumin) solution into the air pouch of immunized rats was inhibited dose-dependently by treatment with PAF antagonists 180) in parallel with the decrease in neutrophil chemotactic activity in the pouch fluid. 3 Four hours after injection of the antigen solution into the air pouch of immunized and nonimmunized rats, there was no significant difference between the two groups in the number of total leucocytes, neutrophils, mononuclear cells and eosinophils in the pouch fluid. However, when the infiltrated leucocytes were incubated in medium, chemotactic factor production by leucocytes from immunized rats was greater than that from non-immunized rats. 4 When leucocytes from non-immunized rats were preincubated for various periods in the medium containing 10 or 50 nM of PAF, washed, and further incubated in the medium containing no PAF, chemotactic factor production was not stimulated. 5The increase in the chemotactic activity in the conditioned medium was not suppressed by the 5-lipoxygenase inhibitor, AA861. In addition, the chemotactic activity in the conditioned medium was not inhibited by the PAF antagonists. 6 Incubation of the infiltrated leucocytes in the medium containing the protein synthesis inhibitor, cycloheximide, inhibited chemotactic factor production in a concentration-dependent manner in parallel with the decrease in uptake of [3H]-leucine into the acid-insoluble fraction of leucocytes. 7 Separation of the chemotactic activity in the conditioned medium by isoelectric focusing revealed that the leucocyte infiltrated into the pouch fluid produce two kinds of factors, viz. leucocyte-derived neutrophil chemotactic factor-i (LDNCF-1) and LDNCF-2 of which pI values are 4-5 and above 8, respectively. 8 The results indicate that PAF has no significant role in leucocyte activation to produce chemotactic factors, and that neutrophil chemotactic factors produced by infiltrated leucocytes are not PAF or leukotriene B4 but are produced through a protein synthesis mechanism. 9 The mechanism of action of PAF antagonists on neutrophil infiltration into the inflammatory locus is discussed.

“…During the course of experiments to identify the difference between allergic and non-allergic inflammation employing an air pouch-type inflammation model in rats 1985;Tsurufuji et al, 1982;Hirasawa et al, 1986;Watanabe et al,1987;1990), focused especially on the qualitative difference in the function of infiltrated leucocytes, we found (Watanabe et al, 1994) that the leucocytes ' Author for correspondence. infiltrated into the pouch fluid in the allergic inflammation model are much more active than those in the non-allergic inflammation model with respect to neutrophil chemotactic factor production.…”

Section: Introductionmentioning

confidence: 99%

Possible roles of protein kinases in neutrophil chemotactic factor production by leucocytes in allergic inflammation in rats

Tanabe

Kondoh

et al. 1994

British J Pharmacology

Self Cite

1 In an air pouch-type allergic inflammation model in rats, leucocytes that had infiltrated into the pouch fluid collected 4 h after the antigen challenge produced proteinaceous chemotactic factors for neutrophils when they were incubated in the medium. 2 To clarify the mechanism of activation of the infiltrated leucocytes in producing these factors, the effects of protein kinase inhibitors on neutrophil chemotactic factor production were examined. 3 When the infiltrated leucocytes were incubated for 4 h in medium containing the non-selective protein kinase inhibitor K-252a (1-100 ng ml-', 2.14-214 nM), the tyrosine kinase inhibitor genistein (1-50 1tgml', 3.7-185 p M), and the more selective protein kinase C inhibitor H-7 (5-100 A gml', 13.7-274 gM); neutrophil chemotactic activity in the conditioned medium was decreased in a concentration-dependent manner, but the adenosine 3':5'-cyclic monophosphate (cAMP)-dependent protein kinase inhibitor H-89 (1-10Ongml1', 2.24-2240nM) showed no effect.4 Isoelectric focusing of the conditioned medium revealed that the leucocytes produced two neutrophil chemotactic factors, leucocyte-derived neutrophil chemotactic factor (LDNCF) 1 and LDNCF-2. Treatment of the leucocytes with K-252a, genistein, and H-7, but not H-89, inhibited production of both LDNCF-1 and LDNCF-2. 5 These results suggest that activation of tyrosine kinase and protein kinase C, but not cAMPdependent protein kinase, is responsible for the production of LDNCF-1 and LDNCF-2. 6 The steroidal anti-inflammatory drug dexamethasone and the protein synthesis inhibitor cycloheximide inhibited neutrophil chemotactic factor production in a concentration-dependent manner. Timecourse experiments showed that the inhibitory effect by dexamethasone was apparent even 30 min after the incubation. 7 Mechanism for inhibiting the production of LDNCF-1 and LDNCF-2 by dexamethasone is also discussed.