title: Chemotactic mediator requirements in lung injury following skin burns in rats.
abstract: Partial-thickness skin burns have been shown to induce neutrophil-dependent microvascular injury both locally (skin) and systemically (lung). In the present study, interventional measures to block inflammatory chemoattractants were employed to define the pathophysiologic role of these mediators in the development of secondary lung injury following thermal injury of skin. Rats were treated with blocking antibodies to either C5a or to the alpha-chemokines, keratinocyte-derived cytokine (KC), or macrophage inflammatory protein-2 (MIP-2). To study the role of platelet activating factor, a receptor antagonist (PAF-Ra) was utilized. The development of lung vascular injury following thermal injury to skin was significantly attenuated by treatment with anti-C5a (84%), anti-KC (67%), and anti-MIP-2 (77%), but treatment with PAF-Ra had no protective effects. Protective interventions were paralleled by significant reductions in the tissue buildup of myeloperoxidase. When bronchoalveolar lavage fluids from thermally injured rats were evaluated, elevations in TNF;ZA and IL-1 were found and were determined to be C5a-dependent (but unaffected by treatment with PAF-Ra). These studies indicate that lung tissue injury after thermal skin burns is dependent on chemotactic mediators. The data also suggest that lung expression of TNFalpha and IL-1 after thermal injury of skin is C5a-dependent.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
authors.forename: M T
authors.initials: MT
authors.lastname: Piccolo
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: P
authors.initials: P
authors.lastname: Sannomiya
authors.forename: N S
authors.initials: NS
authors.lastname: Piccolo
authors.forename: M S
authors.initials: MS
authors.lastname: Piccolo
authors.forename: T E
authors.initials: TE
authors.lastname: Hugli
authors.forename: P A
authors.initials: PA
authors.lastname: Ward
authors.forename: G O
authors.initials: GO
authors.lastname: Till
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002056:Burns / Q000201:enzymology / Q000503:physiopathology*; D002199:Capillary Permeability; D054426:Chemokine CXCL2; D018925:Chemokines; D002630:Chemotactic Factors / Q000276:immunology / Q000502:physiology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects / Q000502:physiology*; D015936:Complement C5a / Q000276:immunology / Q000502:physiology; D016207:Cytokines / Q000276:immunology / Q000502:physiology; D007375:Interleukin-1 / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000201:enzymology / Q000503:physiopathology; D008171:Lung Diseases / Q000201:enzymology / Q000503:physiopathology*; D055370:Lung Injury; D008297:Male; D015846:Monokines / Q000276:immunology / Q000502:physiology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D009195:Peroxidase / Q000378:metabolism; D010972:Platelet Activating Factor / Q000276:immunology / Q000502:physiology; D010980:Platelet Membrane Glycoproteins / Q000037:antagonists & inhibitors; D011817:Rabbits; D051381:Rats; D020318:Rats, Long-Evans; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D012867:Skin / Q000293:injuries*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019138:Antibodies, Blocking; D054426:Chemokine CXCL2; D018925:Chemokines; D002630:Chemotactic Factors; D016207:Cytokines; D007375:Interleukin-1; D015846:Monokines; D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D014409:Tumor Necrosis Factor-alpha; C039351:platelet activating factor receptor; C074302:keratinocyte-derived chemokines; D015936:Complement C5a; D009195:Peroxidase