The role of complement, platelet‐activating factor and leukotriene B 4 in a reversed passive Arthus reaction

The role of the adhesion glycoproteins CD 18 and intercellular adhesion molecule‐1 (ICAM‐1) in inflammatory responses produced during a reversed passive Arthus (RPA) reaction and induced by zymosan and zymosan‐activated plasma (ZAP) were studied in rabbit skin. Oedema formation and haemorrhage were quantified by measuring accumulation of 125I‐albumin and 111In‐labelled red blood cells (111In‐RBC) respectively. Monoclonal antibody (mAb) R15.7 (anti‐CD18), administered intravenously, abolished accumulation of 125I‐albumin and 111In‐RBC in dermal RPA reactions and in response to locally injected zymosan and ZAP. When administered intravenously, the mAb RR1/1 (anti‐ICAM‐1) suppressed 125I‐albumin and 111In‐RBC accumulation in dermal RPA reactions and at sites treated with zymosan and ZAP. Oedema formation in response to platelet‐activating factor (PAF) and bradykinin (BK) either in the presence or absence of prostaglandin E2 (PGE2) were not affected by mAb R15.7 or by mAb RR1/1.1.1. We conclude that oedema formation and haemorrhage associated with RPA reactions and in responses to zymosan and ZAP are completely CD 18‐dependent, and are mediated, at least in part, via ICAM‐1. Responses to the neutrophil‐independent oedema forming mediators, PAF and BK are not dependent upon CD 18 or ICAM‐1.

Section: Monoclonal Antibodiesmentioning

confidence: 99%

Role of adhesion glycoproteins CD 18 and intercellular adhesion molecule‐1 in complement‐mediated reactions of rabbit skin

Norman

Argenbright

Williams

et al. 1994

“…The phospholipid platelet-activating factor (PAF) appears to play an important role in the development of the Arthus reaction as PAF antagonists, administered locally or i.v., have been shown to reduce oedema formation associated with RPA reactions in rabbit and rat skin (Deacon et al, 1986;Issekutz & Szejda, 1986;Williams et al, 1986;Warren et al, 1989;Hellewell, 1990;Rossi et al, 1992). Neutrophil depletion has been shown to suppress oedema formation in RPA reactions in rat skin, an inhibition that is reported to be partially reversed by local injection of neutrophils (Warren et al, 1989).…”

Section: Introductionmentioning

confidence: 99%

“…This model of vascular injury is initiated by the local deposition of immune complexes within the vessel wall and previous reports have demonstrated the importance of neutrophils (Humphrey, 1955a;Cochrane & Janoff, 1974;Warren et al, 1989) and complement fragments such as C5a (Cochrane et al, 1970;Cochrane & Janoff, 1974;Lewis & Turk, 1975;Jose et al, 1983;Yeh et al, 1991;Rossi et al, 1992). The role of platelets and their contribution to the development of the reaction remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Role of platelet‐activating factor (PAF) in platelet accumulation in rabbit skin: effect of the novel long‐acting PAF antagonist, UK‐74,505

Pons

Rossi

Norman

et al. 1993

Self Cite

1 The contribution of platelet-activating factor (PAF) to platelet deposition and oedema formation induced by exogenous soluble mediators, zymosan particles and associated with a reversed passive Arthus (RPA) reaction in rabbit skin was investigated by use of a novel long-acting PAF receptor antagonist, UK-74,505. 2 Oedema formation and platelet accumulation were simultaneously measured by i.v. injection of ['25l-albumin and "'In-labelled rabbit platelets. UK-74,505 was either administered i.v. or used to pretreat radiolabelled platelets in vitro before their injection into recipient animals. Platelets pretreated with UK-74,505 were also labelled with the fluorescent calcium indicator, Fura-2, to assess their ex vivo reactivity to PAF at the end of the in vivo experiment.3 UK-74,505 (0.5mgkg-'), administered i.v., inhibited PAF-induced oedema formation, but did not affect oedema induced by zymosan particles, bradykinin (BK), histamine, formyl-methionyl-leucylphenylalanine (FMLP), zymosan-activated plasma (ZAP, as a source of C5a des Arg), leukotriene B4 (LTB4) or interleukin-8 (IL-8). 4 UK-74,505, administered i.v. also suppressed the small platelet accumulation induced by exogenous PAF, but had no effect on accumulation induced by IL-8 or ZAP. Although oedema induced by zymosan was not affected by i.v. UK-74,505, zymosan-induced platelet accumulation was significantly attenuated by the antagonist. 5 The RPA reaction in rabbit skin was associated with marked oedema formation and platelet accumulation which were both inhibited by i.v. UK-74,505. 6 In vitro, UK-74,505 inhibited aggregation and the increase in intracellular calcium concentration induced by PAF in rabbit washed platelets in a concentration-dependent manner (ICM = 1.6 x I0O-M and 1.1 x 10-8 M, respectively). Platelets pretreated with 10-6 M UK-74,505, and maintained at 37°C, were unresponsive to PAF, whilst responding normally to thrombin, for up to 4 h. 7 In a second series of in vivo experiments, platelets were labelled with "'In and loaded with Fura-2. The platelets were then pretreated with 10-6 M UK-74,505, washed, and injected into recipient rabbits. These platelets, prepared from blood samples taken at the end of the in vivo experiments, exhibited an 80% reduction in their response to PAF as measured ex vivo with Fura-2. However, in contrast to the effects of i.v. UK-74,505, platelets pretreated with the antagonist did accumulate effectively in the RPA reaction, a significant reduction only being observed in responses at the lowest antibody dose. In addition, pretreatment of platelets had no effect on the small platelet accumulation induced by PAF. 8 These results suggest that PAF is an important mediator of oedema formation and platelet accumulation in the RPA reaction in rabbit skin. However, they question the role of PAF receptors on platelets in this model. The results also indicate that PAF may be involved in platelet accumulation induced by zymosan in rabbit skin.

“…This model is a good counterpart of immune complex peritonitis, when developed in the peritoneal cavity. The sequence of events that occur in the RPA reaction includes formation of immune complexes in the microvessel wall, activation of the complement cascade, migration and adherence of polymorphonuclear leukocytes (PMN) to the endothelial cells, which results in an increase of microvascular permeability (Wedmore & Williams, 1981), and release of PAF from neutrophils which acts on endothelial cells to cause further leakage (Hellewell & Williams, 1986;Warren et al, 1989a;Rossi et al, 1992;Tavares de Lima et al, 1992). Since tissue injury in RPA is I Author for correspondence.…”

Section: Introductionmentioning

confidence: 99%

“…Recent therapeutic approaches to the Arthus reaction focus on the use of recombinant soluble human complement receptor type I (Rossi et al, 1992) to control the activation of the complement cascade, the utilization of a recombinant soluble form of human Fc-yRII (Fc-yR, receptor for the Fc portion of IgG) genetically engineered to interfere with neutrophil activation via Fc-yRII, and the ensuing release of inflammatory mediators (Ierino et al, 1993); and the utilization of recombinant selectin chimeric molecules to block PMN recruitment (Mulligan et al, 1993). Another step for pharmacological modulation might be the antagonism of mediators released from PMN that could be particularly active either on their own or because of their central position Brfth Journal of Pharmacology (1995) 114.…”

Section: Introductionmentioning

confidence: 99%

Platelet‐activating factor: the effector of protein‐rich plasma extravasation and nitric oxide synthase induction in rat immune complex peritonitis

Steil¹,

Garcia‐Rodriguez²,

Crespo³

1995

1 The involvement of platelet-activating factor (PAF) in immune complex-induced/polymorphonuclearmediated tissue injury was studied by use of a reverse passive Arthus (RPA) model in the peritoneal cavity of rats. 2 Extravasation of protein-rich plasma, accumulation of polymorphonuclear leukocytes (PMN), and the production of nitric oxide (NO) by resident peritoneal mononuclear phagocytes were assayed. 3 Treatment of rats with either UR-12460 or BB-823, two compounds which possess different chemical structures, but elicit the same antagonistic effect on the PAF receptor, abrogated protein-rich plasma extravasation. In contrast, they did not show any effect on the accumulation of PMN. 4 Inhibition of NO production with both N1-mono methyl-L-arginine and N0-nitro-L-arginine failed to prevent protein-rich plasma extravasation. 5 The production of NO by peritoneal adherent cells following RPA was measured in cells maintained for 2 to 28 h in culture, and it was significantly increased in cells removed as early as 15 min after RPA induction, as compared to controls. 6 Addition of 10 nM PAF to the culture medium reduced the generation of NO by peritoneal cells from RPA rats, whereas this mediator enhanced NO production in cells from naive control animals. 7 Treatment with either UR-12460 or BB-823 prior to the induction of RPA produced an almost complete inhibition of NO production. 8 Assay of nitric oxide synthase activity in cell homogenates from peritoneal cells showed that the activity was due to the inducible form of the enzyme. 9 Study by Northen blotting of mRNA coding for the inducible NO synthase (iNOS) showed transcription at 6 and 18 h after the induction of RPA, which was inhibited in UR-12460-treated rats. 10 These data indicate that PAF is the main mediator of the early plasma leakage observed in RPA, and also that PAF is implicated in the triggering of long-term changes via induction of specific genes, as judged from its ability to promote the expression of iNOS.