PMID- 9042155
OWN - NLM
STAT- MEDLINE
DCOM- 19970318
LR  - 20131121
IS  - 0023-6837 (Print)
IS  - 0023-6837 (Linking)
VI  - 76
IP  - 2
DP  - 1997 Feb
TI  - Neutrophils and reactive oxygen intermediates mediate glucan-induced pulmonary 
      granuloma formation through the local induction of monocyte chemoattractant 
      protein-1.
PG  - 191-201
AB  - Monocyte chemoattractant protein-1 (MCP-1), which is required for full 
      development of glucan-induced granulomas, in the rat, is expressed in the walls 
      of blood vessels at sites of glucan embolization. Early (1 hour) vessel wall 
      expression of MCP-1 is temporally and anatomically linked to the transient 
      accumulation of neutrophils, even though these cells are not present within 
      definitive lesions. To ascertain the potential pathophysiologic role of 
      neutrophils in glucan-induced granuloma formation, rats were neutrophil-depleted 
      using specific antiserum. There was a marked reduction in mean granuloma size and 
      number in neutrophil-depleted animals when compared with neutrophil-sufficient 
      controls. To determine potential mechanisms through which neutrophils may 
      participate in granuloma formation, the antioxidant enzymes superoxide dismutase 
      and catalase were administered to neutrophil-sufficient animals that had received 
      glucan. Superoxide dismutase treatment did not reduce granuloma formation, 
      whereas catalase treatment resulted in decreased granuloma size, suggesting that 
      H2O2 plays an important role in this process. The local expression of MCP-1 mRNA 
      and protein, as determined by in situ hybridization and immunohistochemical 
      analysis, respectively, was decreased in both neutrophil-depleted and 
      catalase-treated animals but not in superoxide dismutase-treated rats. Quiescent 
      human umbilical vein endothelial cells incubated with either H2O2 or activated 
      neutrophils secreted MCP-1. These data indicate that neutrophils and H2O2 are 
      required for both full granuloma development and early blood vessel 
      wall-associated MCP-1 expression after glucan infusion. These in vivo data, 
      coupled with in vitro data that indicate that both catalase-sensitive reagent 
      H2O2 and neutrophil-derived reactive oxygen intermediates (ie, H2O2) can induce 
      MCP-1 secretion by human umbilical vein endothelial cells, support the hypothesis 
      that neutrophils and neutrophil-derived products (H2O2) influence granuloma 
      formation through induction of local MCP-1 expression.
FAU - Kilgore, K S
AU  - Kilgore KS
AD  - Department of Pathology, University of Michigan Medical School, Ann Arbor, USA.
FAU - Imlay, M M
AU  - Imlay MM
FAU - Szaflarski, J P
AU  - Szaflarski JP
FAU - Silverstein, F S
AU  - Silverstein FS
FAU - Malani, A N
AU  - Malani AN
FAU - Evans, V M
AU  - Evans VM
FAU - Warren, J S
AU  - Warren JS
LA  - eng
GR  - 5T32-HL07517/HL/NHLBI NIH HHS/United States
GR  - HL48287/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 0 (Chemokine CCL2)
RN  - 0 (Glucans)
RN  - 0 (RNA, Messenger)
RN  - BBX060AN9V (Hydrogen Peroxide)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Chemokine CCL2/analysis/*biosynthesis
MH  - Glucans
MH  - Granuloma/chemically induced/*etiology/metabolism
MH  - Humans
MH  - Hydrogen Peroxide/*metabolism
MH  - Immunohistochemistry
MH  - In Situ Hybridization
MH  - Lung/chemistry/pathology
MH  - Lung Diseases/*etiology/metabolism
MH  - Male
MH  - Neutrophils/*physiology
MH  - RNA, Messenger/biosynthesis
MH  - Rats
EDAT- 1997/02/01 00:00
MHDA- 1997/02/01 00:01
CRDT- 1997/02/01 00:00
PHST- 1997/02/01 00:00 [pubmed]
PHST- 1997/02/01 00:01 [medline]
PHST- 1997/02/01 00:00 [entrez]
PST - ppublish
SO  - Lab Invest. 1997 Feb;76(2):191-201.