Neutrophils are involved in the increased vascular permeability produced by activated complement in man

Williamson, Lorna M.; Sheppard, K; Davies, J. M.; Fletcher, J.

doi:10.1111/j.1365-2141.1986.tb04131.x

Cited by 15 publications

(8 citation statements)

References 20 publications

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“…This information suggests that non-leucocyte dependent mechanisms increase IF volume in immature rats (as in adult mice). However, leucocytes cannot be excluded entirely since leucocyte adhesion to the endothelium, as observed in the present study in immature rats, may be sufficient to increase permeability without any migration of leucocytes through the vessel walls (Williamson et al, 1986). When adult rats are given hCG together with a fi-adrenergic agonist , no carbon-labelled vessels were observed despite marked intravascular accumulation of leucocytes (Bergh & Damber, 1987b).…”

Section: Discussionmentioning

confidence: 55%

Age‐related differences in testicular microcirculation

1990

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Different aspects of testicular microcirculation were studied in rats aged 20, 24 or 90 days, in order to determine if maturational changes in the testis could influence its vasculature. Using laser Doppler flowmetry, it was found that vasomotion was not present in 20-day-old rats, but it could be induced by hCG-treatment given 32 h prior to flow measurements. In rats aged 24 days vasomotion was present in the testis but it was not influenced by hCG treatment, in contrast to adult rats in which testicular vasomotion disappeared after hCG treatment. In all age-groups, hCG treatment induced an increase in testicular interstitial fluid (IF) volume, which was most pronounced in young rats. In young rats, as in adults, there was an increase in the volume density of polymorphonuclear (PMN) leucocytes in testicular blood vessels after hCG treatment. However, rats aged 20 or 24 days did not exhibit any significant extravascular migration of leucocytes as occurred in adult rat testis after hCG injection. The deposition of colloidal carbon particles observed in adult rats after hCG-treatment was also not seen in young rats. It is concluded that the vasculature of the immature rat testis responds to hCG stimulation with an increase in IF volume. However, when compared to adult rats, different mechanisms may be operating because no evidence for opening of inter-endothelial cell gaps was observed in the testis of young rats.

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Section: Discussionmentioning

confidence: 55%

Age‐related differences in testicular microcirculation

1990

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“…These two mechanisms were initially ' Author for correspondence. described in rabbit skin (Wedmore & Williams, 1981a) but were later found to occur in hamsters (Bjork & Smedegard), 1983), rats (Mulligan et al, 1992b), mice (Perretti et al, 1993) and also in man (Williamson et al, 1986).…”

Section: Introductionmentioning

confidence: 99%

Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea‐pig skin: contribution of neutrophils and endogenous mediators

Teixeira

Fairbairn

Norman

et al. 1994

British J Pharmacology

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1 Mediators of inflammation can increase vascular permeability in at least two different ways: by acting directly on endothelial cells or, indirectly, through an incompletely understood mechanism, dependent on circulating neutrophils. Neutrophil-dependent oedema formation has been described in the skin of rabbits, rats, hamsters, mice and man. In contrast, we presented evidence in a previous study that local oedema formation induced by i.d. injection of chemoattractants in guinea-pig skin was neutrophil-independent. In the present study, we sought evidence of neutrophil-dependent oedema formation in immune-complex-mediated vasculitis, the reversed passive Arthus (RPA) reaction, in guinea-pig skin. We also investigated whether haemorrhage in the RPA reaction was neutrophildependent (as it is in other species) and the role of endogenous mediators of inflammation (prostaglandins, nitric oxide, histamine, PAF and leukotrienes) in contributing to the local inflammatory response. 2 In the RPA reaction, most oedema formation occurred over the first 60 min whereas "'In-neutrophil accumulation was still increasing from 60 to 240 min. The different kinetics of these two events suggested that they may be dissociated.3 Oedema formation was partially inhibited by a long-acting PAF antagonist (UK-74,505) and an HI histamine receptor antagonist (mepyramine) but not by a 5-lipoxygenase inhibitor (ZM 230487). A nitric oxide synthesis inhibitor (NW-nitro-L-arginine methyl ester, L-NAME) suppressed oedema formation by 68% whereas a cyclo-oxygenase inhibitor suppressed oedema by 27%. 4 "'In-neutrophil accumulation in the RPA reaction was partially suppressed by UK-74,505. In contrast, ZM 230487 was without effect at doses which abrogated arachidonic acid-induced "'Inneutrophil accumulation. 5The anti-CD18 monoclonal antibody, (mAb) 6.5E F(ab')2, effectively inhibited "'In-neutrophil accumulation induced by PAF, zymosan-activated plasma (ZAP) and in the RPA reaction. However, oedema formation measured in the same sites was not altered. In contrast, oedema formation in the RPA reaction was partially suppressed by 6.5E whole mAb which was 2.5 times more potent than 6.5E F(ab')2 at inhibiting guinea-pig neutrophil adhesion to protein-coated plastic. Haemorrhage induced by PAF and in the RPA reaction was significantly inhibited by 6.5E F(ab')2 pretreatment. 6 We conclude that in the RPA reaction in guinea-pig skin, oedema formation is partially neutrophildependent as assessed by using an anti-CD18 mAb, whereas ZAP-induced oedema formation is neutrophil-independent. Haemorrhage was also dependent on neutrophil accumulation. In addition, our studies support a role for PAF in mediating both oedema formation and "'In-neutrophil accumulation in the RPA reaction. Endogenous release of histamine also appears to be important in mediating oedema formation suggesting that mast cells play a critical role in increases of vascular permeability in inflammatory reactions in guinea-pig skin. Moreover, our results confirm previous findings which suggest...

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“…Studies in man have shown that the wheal response to i.d. injection of zymosan-activated autologous serum (ZAS), as a source of C5a des Arg, was attenuated in neutropaenic subjects but only marginally reduced by an anti-histamine (Williamson et al, 1986). In contrast, i.d.…”

Section: Introductionmentioning

confidence: 99%

Role of CD18 in the accumulation of eosinophils and neutrophils and local oedema formation in inflammatory reactions in guinea‐pig skin

Teixeira

Reynia

Robinson³

et al. 1994

British J Pharmacology

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Intradermal injection of the complement fragment C5a des Arg induces local oedema formation that, in rabbits and man, is dependent on circulating neutrophils. Monoclonal antibodies to the leukocyte adhesion molecule CD11/CD18 block neutrophil accumulation and prevent neutrophil‐dependent oedema formation. The role of CD11/CD18 in mediating eosinophil accumulation in vivo is less established. In this study we have used an anti‐human CD18 monoclonal antibody, 6.5E, to investigate the neutrophil‐dependency of oedema formation induced by C5a des Arg in guinea‐pig skin. We also studied the role of CD18 in mediating eosinophil accumulation in the same model. Stimulated adhesion of 111In‐labelled guinea‐pig neutrophils and eosinophils to serum‐coated plastic was inhibited in a dose‐dependent manner by 6.5E suggesting that the monoclonal antibody recognizes and blocks the guinea‐pig CD18 adhesion molecule. The accumulation of 111In‐labelled neutrophils induced by zymosan‐activated plasma (ZAP, as a source of C5a des Arg) in skin sites was reduced by up to 89% in animals treated intravenously with F(ab')2 fragments of 6.5E. ZAP‐induced accumulation of 111In‐labelled eosinophils was also greatly reduced (by up to 78%) by treatment with 6.5E. Despite the inhibition of ZAP‐induced neutrophil accumulation by 6.5E, local oedema formation in the same skin sites was unaffected, except at the top dose of ZAP, by treatment with the anti‐CD18 monoclonal antibody, suggesting that the oedema response was largely neutrophil‐independent. Indeed, ZAP‐induced oedema formation was reduced by up to 81% by the H1 receptor antagonist, mepyramine. Accumulation of 111In‐labelled eosinophils in a passive cutaneous anaphylactic (PCA) reaction was also blocked by treatment with 6.5E, while oedema formation in the same skin sites was unaffected. Intradermal injection of cationic protein‐containing extracts of Schistosoma mansoni larvae also induced the accumulation of 111In‐labelled neutrophils and eosinophils which was abrogated by intravenous 6.5E. In contrast, extract‐induced local oedema formation was similar in control and 6.5E‐treated guinea‐pigs. In summary, the local accumulation of radiolabelled neutrophils at sites of inflammation in guinea‐pig skin was dependent on the adhesion molecule CD18 while, in contrast, there was no evidence for neutrophil‐dependent oedema formation in this species. Accumulation of radiolabelled eosinophils was also dependent on CD18.

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Neutrophils are involved in the increased vascular permeability produced by activated complement in man

Cited by 15 publications

References 20 publications

Age‐related differences in testicular microcirculation

Age‐related differences in testicular microcirculation

Studies on the mechanisms involved in the inflammatory response in a reversed passive Arthus reaction in guinea‐pig skin: contribution of neutrophils and endogenous mediators

Role of CD18 in the accumulation of eosinophils and neutrophils and local oedema formation in inflammatory reactions in guinea‐pig skin

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