Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

Stevens, John H.; O’Hanley, P; Shapiro, Jeffrey; Mihm, Frederick G.; Satoh, Paul S.; Collins, John A.; Raffin, Thomas A.

doi:10.1172/jci112506

Cited by 249 publications

(104 citation statements)

References 17 publications

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“…Septic primates or rats treated with anti-C5a Abs have reduced pulmonary edema and lung injury (73,74). With immune complex-mediated lung injury, intratracheal administration of anti-C5a reduces lung inflammation in rats (75).…”

Section: Discussionmentioning

confidence: 99%

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

Drouin¹,

Kildsgaard²,

Haviland³

et al. 2001

The Journal of Immunology

196

149

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The presence of the complement-derived anaphylatoxin peptides, C3a and C5a, in the lung can induce respiratory distress characterized by contraction of the smooth muscle walls in bronchioles and pulmonary arteries and aggregation of platelets and leukocytes in pulmonary vessels. C3a and C5a mediate these effects by binding to their specific receptors, C3aR and C5aR, respectively. The cells that express these receptors in the lung have not been thoroughly investigated, nor has their expression been examined during inflammation. Accordingly, C3aR and C5aR expression in normal human and murine lung was determined in this study by immunohistochemistry and in situ hybridization. In addition, the expression of these receptors was delineated in mice subjected to LPS- and OVA-induced models of inflammation. Under noninflamed conditions, C3aR and C5aR protein and mRNA were expressed by bronchial epithelial and smooth muscle cells of both human and mouse lung. C3aR expression increased significantly on both bronchial epithelial and smooth muscle cells in mice treated with LPS; however, in the OVA-challenged animals only the bronchial smooth muscle cells showed increased C3aR expression. C5aR expression also increased significantly on bronchial epithelial cells in mice treated with LPS, but was not elevated in either cell type in the OVA-challenged mice. These results demonstrate the expression of C3aR and C5aR by cells endogenous to the lung, and, given the participation of bronchial epithelial and smooth muscle cells in the pathology of diseases such as sepsis and asthma, the data suggest a role for these receptors during lung inflammation.

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Section: Discussionmentioning

confidence: 99%

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

Drouin¹,

Kildsgaard²,

Haviland³

et al. 2001

The Journal of Immunology

196

149

View full text Add to dashboard Cite

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“…Conversely, complement blockade or depletion was beneficial in different animal models of sepsis-ARDS, and dialysis with PAN (as opposed to cuprophane) was associated with faster recovery from ARF in the rate [6,7,8]. In vivo, a specific blockade of factor D activity inhibits complement activation by the alternative pathway [9].…”

Section: Discussionmentioning

confidence: 99%

Complement depletion during haemofiltration with polyacrilonitrile membranes

Gasche¹,

Pascual²,

Suter³

et al. 1996

Nephrology Dialysis Transplantation

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Background. Polyacrylonitrile (PAN, AN69®) dialysis membranes have been shown to improve the outcome of critically ill patients. Factor D is an essential enzyme of the alternative pathway of complement and is increased during renal failure. On the other hand the contact of blood with biomaterials activates the complement cascade through the alternative pathway. PAN niters adsorb factor D which looses its enzymatic activity whilst bound to the membrane [1]; the complement alternative pathway function of serum exposed to PAN filters is greatly diminished and restored after addition of purified factor D [1]. The aim of our study was to measure the time course of factor D adsorption and its blood concentration during CVVH in critically ill patients with acute renal failure. Methods. We studied seven critically ill patients with ARF before, during and after continuous veno-venous haemofiltration (CWH) with AN69.

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“…These latter two cytokines also induce the expression of adhesion molecules on the surfaces of endothelial cells which will result in adherence of PMN to the endothelium (Cotran & Pober, 1989;Ward & Marks, 1989;Mantovani & Dejana, 1989;Di Giovani & Duff, 1990). These adherent PMN, when activated by a variety of agonists including C5a, and platelet activating factor, may mediate blood vessel wall injury by the production of lyososomal proteases and toxic oxygen radicals (Stevens et al, 1986;Tonnesen et al, 1984;Jacobs et al, 1980;Perez et al, 1983).…”

mentioning

confidence: 99%

The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant Interleukin-2

Baars

Hack²,

Pinedo³

et al. 1992

Br J Cancer

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Summary The toxicity due to interleukin-2 (IL-2) strongly resembles the clinical picture seen during septic shock. In septic shock activation of polymorphonuclear neutrophils (PMN) and the complement system contribute significantly to the pathophysiology of the condition. We therefore investigated whether similar events contributed to the toxicity observed with IL-2.Four patients received seven cycles of escalating dose IL-2 (18.0 to 72.0 x 106 IU m-2 day-') and 16 were treated with 20 cycles of fixed dose IL-2 (12.0 or 18.0 x 106 IU m-2 day-'). Toxicity, as judged by hypotension (P = <0.005) and capillary leakage (fall in serum albumin 18.2 vs 4.0 gm 1'; P = <0.0005 and weight gain 4.0 vs 1.2 kg; P = <0.025) were worse with the esc. dose protocol.PMN became activated following IL-2 with mean peak elastase/a,-antitrypsin (Ea,A) and lactoferrin values of 212 (SEM = 37) and 534 (SEM = 92) ng ml-' respectively occurring 6 h after the IL-2. Peak values for the esc. dose IL-2 group being generally higher than 500 ng ml-'. Activation of the complement cascade was evidenced by a dose dependent elevation of peak C3a values (fixed dose 9.1 (SEM = 0.6); esc. dose 25.7 (SEM = 6.33); P = <0.005) on day 5 of IL-2.There was a significnt correlation between C3a levels and the degree of hypotention during the first 24 h after IL-2 (r = 0.91) and parameters of capillary leakage such as weight gain and fall in serum albumin (r = 0.71).These data suggest that activation of PMN initiates endothelial cell damage which subsequently leads to activation of the complement cascade. This latter system then contributes to the haemodynamic changes and capillary leakage seen in IL-2 treated patients.

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Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

Cited by 249 publications

References 17 publications

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

Expression of the Complement Anaphylatoxin C3a and C5a Receptors on Bronchial Epithelial and Smooth Muscle Cells in Models of Sepsis and Asthma

Complement depletion during haemofiltration with polyacrilonitrile membranes

The activation of polymorphonuclear neutrophils and the complement system during immunotherapy with recombinant Interleukin-2

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