Mitochondrial damage-associated molecular patterns from XXXX suppress pulmonary immune responses via formyl peptide receptors 1 and 2.

@entity1 @entity6722 @entity5038 @entity174 @entity55 @entity19 @entity794 @entity1359 @entity4515 @entity71666 @entity4621 @entity358 @entity35 @entity51758 @entity435 @entity130
BACKGROUND: No known biologic mechanisms link tissue injury with @entity55 ( @entity55 ). Neutrophils (PMNs) are innate immune cells that clear bacteria from the lung by migration toward chemoattractants and killing bacteria in neutrophil extracellular traps (NETs). We predicted that tissue injury would suppress PMN antimicrobial function in the lung. We have also shown that mitochondria-derived damage-associated molecular pattern molecules from the bone can alter PMN phenotype and so hypothesized that @entity435 peptides (FPs) from @entity174 predispose to @entity55 by suppressing PMN activity in the lung. METHODS: Animal studies involved the following. (1) @entity35 were divided into three groups (10 per condition) as follows: (a) saline injection in the thigh (b) @entity794 (SA, 3 * 10) injected intratracheally, or (c) pseudofracture (PsFx; bone supernatant injected in the thigh) plus intratracheally injected SA. (2) @entity35 were divided into four groups as follows: (a) control, (b) @entity358 ( @entity358 ), (c) PsFx, and (d) @entity358 + PsFx. Bronchoalveolar lavage was performed 16 hours later. Clinical studies involved the following. (3) @entity1 bone supernatant was assayed for its @entity5038 ( @entity5038 ) stimulation. (4) @entity130 @entity1 ' PMN (n = 32; mean    SE Injury Severity Score [ISS], 27    10) were assayed for @entity6722 ( @entity6722 ) or treated with @entity1359 ( @entity4515 , @entity4621 ) and analyzed for NET formation. RESULTS: In the animal studies, (1) SA was rapidly cleared by the uninjured @entity19 and PsFx markedly suppressed lung bacterial clearance (p < 0.01). (2a) @entity358 induces PMN traffic to the lung, but PsFx decreases @entity358 -induced PMN traffic (p < 0.01). (2b) SA increased bronchoalveolar lavage PMN, and PsFx decreased that influx (p < 0.01). In the clinical studies, (3) bone supernatant activates PMN both via @entity5038 and @entity51758 . (4) @entity130 decreases PMN @entity6722 to multiple chemokines. Circulating PMNs show NETs spontaneously after @entity130 , but maximal NET formation is markedly attenuated. CONCLUSION: @entity174 may decrease lung bacterial clearance because FP suppresses PMN @entity6722 to other chemoattractants via @entity71666 . @entity130 activates NETosis but suppresses maximal NETosis. @entity174 decrease lung bacterial clearance by multiple mechanisms. @entity55 after @entity174 may reflect damage-associated molecular pattern-mediated suppression of PMN antimicrobial function in the lung.
