title: Divergent effects of activated neutrophils on inflammation, Kupffer cell/splenocyte activation, and lung injury following blunt chest trauma.
abstract: Polymorphonuclear granulocytes (PMNs) have been attributed a primarily deleterious role in the pathogenesis of acute lung injury (ALI). However, evidence exists that PMNs might also act beneficially in certain types of ALI. In this regard, we investigated the role of activated neutrophils in the pathophysiology of lung contusion-induced ALI. We used the model of blunt chest trauma accompanied by PMN-depletion in male C3H/HeN mice. Animals received 25 μg/g body weight PMN-depleting antibody Gr-1 intravenously 48 h before trauma. Bronchoalveolar lavage (BAL) and lung tissue interleukin 6 (IL-6) were similarly elevated in PMN-depleted and control animals after trauma, whereas macrophage inflammatory protein 2 and monocyte chemoattractant protein 1 in BAL and lungs, IL-10 in BAL, and lung keratinocyte chemoattractant (KC) were even further increased in the absence of PMNs. Plasma IL-6 and KC were also increased in response to the insult and even further in the absence of PMNs. Chest trauma induced an enhanced release of IL-6, tumor necrosis factor α, macrophage inflammatory protein 2, monocyte chemoattractant protein 1, and IL-10 from isolated KU, which was blunted in the absence of PMNs. In the presence of PMNs, BAL protein was further increased at 30 h when compared with the 3-h time point, which was not the case in the absence of PMNs. Taken together, in response to lung trauma, activated neutrophils control inflammation including mediator release from distant immune cells but simultaneously mediate pulmonary tissue damage. Thus, keeping in mind potential inflammatory adverse effects, modulation of neutrophil activation or trafficking might be a reasonable therapeutic approach in chest trauma-induced lung injury.
authors.affiliation: Department of Trauma, University of Ulm, Germany. mario-perl@uniklinik-ulm.de
authors.forename: Mario
authors.initials: M
authors.lastname: Perl
authors.forename: Manuel
authors.initials: M
authors.lastname: Kieninger
authors.forename: Markus S
authors.initials: MS
authors.lastname: Huber-Lang
authors.forename: Hans-Jürgen
authors.initials: HJ
authors.lastname: Gross
authors.forename: Max G
authors.initials: MG
authors.lastname: Bachem
authors.forename: Sonja
authors.initials: S
authors.lastname: Braumüller
authors.forename: Florian
authors.initials: F
authors.lastname: Gebhard
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
authors.forename: Markus W
authors.initials: MW
authors.lastname: Knöferl
mesh_terms: D000818:Animals; D001835:Body Weight; D018893:Bronchoalveolar Lavage; D006098:Granulocytes / Q000166:cytology*; D015603:Keratinocytes / Q000166:cytology; D007728:Kupffer Cells / Q000166:cytology*; D055370:Lung Injury / Q000378:metabolism*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000166:cytology*; D009195:Peroxidase / Q000378:metabolism; D013154:Spleen / Q000166:cytology*; D013997:Time Factors; D014949:Wounds, Nonpenetrating / Q000378:metabolism
chemical_list: D009195:Peroxidase