The role of neutrophils in vascular injury: a summary of signal transduction mechanisms in cell/cell interactions

Abstract

Neutrophil-mediated Tissue Injury: the Arthus LesionFollowing the prescient observation of Magendie in 1839 [106] that the second and third intravenous injections of foreign proteins into rabbits were followed by increasing distress, Richet coined the word anaphylaxis in 1902 [135] to describe acute catastrophes mediated by repeated IV injections of antigens (Ag). Arthus [10] then provoked "local anaphylaxis" in rabbits by repeated injections of Ag intradermally: inflammation and necrosis resulted. Opie [122] confirmed that the lesions of Arthus were local Ag-antibody (Ab) reactions in which inflammation was mediated by white cells and that proteolysis was critical. In confirmation (see review [37]) it was found that Arthus lesions could also be provoked by planting Ag in the skin followed by specific Ab IV (the "passive Arthus" reaction) or by injecting Ab in the skin followed by Ag IV (the "reversed passive Arthus" reaction). In each case, one was dealing with the interactions at a surface of neutrophils which had been attracted by inunune complexes localized beneath the endothelium of blood vessels (review [80]). Complement, activated by immune complexes, releases anaphylatoxins (C5a and C3a) which liberate histamine. Histamine, in turn, causes reversible gaps to appear between endothelial cells and, once breached, the junctions permit egress of neutrophils. Stimulated by discrete receptors for C5a, C3a, and IgG (FcRII, FcRIII), neutrophils release mediators of inflammation: reactive oxygen-derived products (03, H202) eicosanoids, and lysosomal enzymes [67]. These products-especially Of, H202 and proteasescause irreversible tissue injury. Predictably, Arthus reactions can be abolished by rendering animals deficient in complement or in neutrophils. Antiproteases or antihistamines are somewhat less effective inhibitors of the Arthus lesion: antiplatelet agents or anticoagulants are useless. It is generally agreed that the local Arthus lesion is one model for immune-complex vasculitis in man which is also due to interactions of neutrophils with immune complexes and complement. In generalized vasculitis of the Arthus type, the homotypic clumping of neutrophils to each other and their heterotypic sticking to endothelial cells is mediated by recep-

Monoclonal antibody to L-selectin attenuates neutrophil accumulation and protects ischemic reperfused cat myocardium.

“…To the best of our knowledge, this is the first observation that L-selectinmediated PMN-endothelium interaction plays a significant role in myocardial reperfusion injury. These results implicate the early rolling phenomenon of PMNs in the microcirculation as a key step in triggering the adherence cascade of events leading to endothelial as (5 'E dysfunction and to neutrophil amplification of the injury to the myocardium. Our data indicate that the DREG-200 cross-reacts significantly with L-selectin on the surface of cat neutrophils, as shown by flow cytometry.…”

Peritoneal and head kidney cell response to intraperitoneally injected yeast glucan in Atlantic salmon, Salmo salar L.

“…Their role in the inflammatory response is uncertain at the present, but they may be involved in the adhesion observed between organs in the peritoneum of fish after vaccination. Neutrophils are associated with tissue damage in mammals because of their ability to produce reactive oxygen molecules (Weissman 1989). The long-term inflammatory reaetion to FIA eombined with a strong neutrophil and thrombocyte response may explain why mineral oil when used as an adjuvant in fish vaeeines gives such adverse side effects in the peritoneum.…”

Blockade of α6 integrin inhibits IL-1β- but not TNF-α-induced neutrophil transmigration in vivo

“…Migration of leukocytes to sites of injury or inflammation is a crucial component of innate and adaptive immunity. However, if inappropriately triggered, excessive or prolonged, this response can be detrimental to the host, leading to the develop-ment of inflammatory disease states such as myocardial infarction, vasculitis, and asthma [1]. Based on detailed in vivo microscopic observations of the microcirculation, it is now generally accepted that within the vascular lumen, stimulated interaction of leukocytes with endothelial cells is mediated by a sequential cascade of reversible and transient adhesive interactions between the two cell types [2].…”