title: Differential effects of macrophage inflammatory chemokine-2 and keratinocyte-derived chemokine on hemorrhage-induced neutrophil priming for lung inflammation: assessment by adoptive cells transfer in mice.
abstract: Prior studies have shown that hemorrhage (Hem) can serve as a priming stimulus for acute lung injury (ALI) triggered by subsequent septic challenge (cecal ligation and puncture, CLP). Furthermore, we have reported that in vivo antibody neutralization of the chemokines, macrophage inflammatory chemokine-2 (MIP-2) and keratinocyte-derived chemokine (KC), immediately after Hem appears to differentially effect the onset of ALI. However, although we hypothesize that this is due to divergent effects of MIP-2 and KC on Hem-induced neutrophil (PMN) priming, this has not been tested. To examine this hypothesis, PMN donor mice were Sham-Hem or Hem for 90 min at 35 +/- 5 mmHg and were then administered anti-MIP- 2 (Hem/anti-MIP2), anti-KC (Hem/anti-KC), or nonspecific immunoglobulin (Ig) G (Hem/IgG) during resuscitation (Ringer's lactate = four times the amount of drawn blood volume). Twenty-four hours post-Hem, the peripheral blood PMN were purified from these donor animals and were introduced into PMN-depleted recipient mice [depleted by prior anti-Gr1 (mouse PMN-specific marker) antibody treatment]. One hour after PMN transfer, recipient mice were subjected to CLP, euthanized 24 h later, and plasma as well as lung tissue samples were collected. PMN influx was assessed by myeloperoxidase assay (MPO; microU/mg protein) and histologically (IL-6, MIP-2, KC, and IL-10 levels) by enzyme-linked immunoabsorbant assay (ELISA; ng/mg). The results show that donor PMN from Hem/IgG but not Sham-Hem mice produce increased PMN influx (increased MPO, increased % esterase+ cells in tissue) into the lung and local tissue inflammation (increased IL-6/MIP-2, decreased IL-10) in PMN-depleted CLP recipient mice, which was attenuated in mice receiving cells from Hem/anti-MIP-2 but not Hem/anti-KC treated donors. Interestingly, although Hem/anti-MIP-2 donor PMN produced comparable effects on blood IL-6/MIP-2 levels, they were ineffective in altering the change in plasma IL-10/KC levels induce by Hem. Taken together, these data demonstrate that Hem-induced priming of PMN not only mediates ALI in the mouse, but also that this process is differentially effected by MIP2 and KC, despite the fact that both signal through CXCR2.
authors.affiliation: Shock-Trauma Research Laboratories in the Division of Surgical Research, Department of Surgery, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Lomas
authors.forename: Chun-Shiang
authors.initials: CS
authors.lastname: Chung
authors.forename: Patricia S
authors.initials: PS
authors.lastname: Grutkoski
authors.forename: Brian W
authors.initials: BW
authors.lastname: LeBlanc
authors.forename: Liz
authors.initials: L
authors.lastname: Lavigne
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reichner
authors.forename: Stephen H
authors.initials: SH
authors.lastname: Gregory
authors.forename: Lesley A
authors.initials: LA
authors.lastname: Doughty
authors.forename: William G
authors.initials: WG
authors.lastname: Cioffi
authors.forename: Alfred
authors.initials: A
authors.lastname: Ayala
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D002432:Cecum / Q000293:injuries; D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines / Q000494:pharmacology*; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology*; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007416:Intestinal Perforation / Q000150:complications; D008026:Ligation; D008171:Lung Diseases / Q000209:etiology*; D019402:Macrophage Inflammatory Proteins / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology* / Q000637:transplantation; D009195:Peroxidase / Q000032:analysis; D016897:Respiratory Burst; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000150:complications*; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications*
chemical_list: D054407:Chemokine CCL4; D054360:Chemokine CXCL1; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; D007074:Immunoglobulin G; D036341:Intercellular Signaling Peptides and Proteins; D019402:Macrophage Inflammatory Proteins; D009195:Peroxidase