PMID- 11641460
OWN - NLM
STAT- MEDLINE
DCOM- 20020102
LR  - 20131121
IS  - 0031-3998 (Print)
IS  - 0031-3998 (Linking)
VI  - 50
IP  - 5
DP  - 2001 Nov
TI  - Monocyte chemoattractant protein-1 and its receptor CCR-2 in piglet lungs exposed 
      to inhaled nitric oxide and hyperoxia.
PG  - 633-40
AB  - Monocyte chemoattractant protein-1 (MCP-1), acting through its C-C chemokine 
      receptor 2 (CCR-2), has important roles in inflammation, angiogenesis, and wound 
      repair. The individual and combined effects of inhaled nitric oxide (NO) and 
      hyperoxia on lung MCP-1 and CCR-2 in relation to lung leukocyte dynamics are 
      unknown. Because MCP-1 gene is up-regulated by oxidants, we hypothesized that 
      inhaled NO with hyperoxia will increase MCP-1 production and CCR-2 expression 
      more than either gas alone. We randomly assigned young piglets to breathe room 
      air (RA), RA+50 ppm NO (RA+NO), O(2), or O(2)+NO for 1 or 5 d before sacrifice. 
      Lungs were lavaged and tissues preserved for hybridization studies, Western 
      blotting, histology, and immunohistochemistry. The results show that lung MCP-1 
      production and alveolar macrophage count were significantly elevated in the 5-d 
      O(2) and O(2)+NO groups relative to the RA group (p < or = 0.05). In contrast, 
      lung CCR-2 abundance was diminished in the O(2) group (p </= 0.05), but not in 
      the O(2)+NO group, compared with the RA group. No difference was detected in any 
      variable studied at 24 h. CCR-2 distribution was similar in all groups with 
      staining of alveolar septa, macrophages, vascular endothelium, and the luminal 
      epithelial surface of airways. We conclude that although hyperoxia increases 
      MCP-1 in young piglet lungs, it also decreases CCR-2 abundance, which may limit 
      participation of MCP-1 in alveolar macrophage recruitment. Inhaled NO, unlike 
      hyperoxia, has no significant independent effect, but its concurrent 
      administration during hyperoxia attenuates the decremental effect of hyperoxia on 
      CCR-2 abundance.
FAU - Ekekezie, I I
AU  - Ekekezie II
AD  - Section of Neonatology, Children's Mercy Hospital and Clinic, University of 
      Missouri at Kansas City School of Medicine, Kansas City, Missouri 64108-9883, 
      USA. IEkekezie@cmh.edu
FAU - Thibeault, D W
AU  - Thibeault DW
FAU - Garola, R E
AU  - Garola RE
FAU - Truog, W E
AU  - Truog WE
LA  - eng
GR  - R-01 HL62079/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  - Pediatr Res
JT  - Pediatric research
JID - 0100714
RN  - 0 (Chemokine CCL2)
RN  - 0 (Interleukin-8)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR2)
RN  - 0 (Receptors, Chemokine)
RN  - 31C4KY9ESH (Nitric Oxide)
SB  - IM
MH  - Administration, Inhalation
MH  - Animals
MH  - Animals, Newborn
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Female
MH  - Hyperoxia/*metabolism
MH  - Immunohistochemistry
MH  - Interleukin-8/genetics
MH  - Lung/drug effects/*metabolism
MH  - Macrophages, Alveolar/metabolism
MH  - Male
MH  - Nitric Oxide/administration & dosage/*pharmacology
MH  - RNA, Messenger/genetics
MH  - Receptors, CCR2
MH  - Receptors, Chemokine/*metabolism
MH  - Swine
EDAT- 2001/10/20 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/20 10:00
PHST- 2001/10/20 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/20 10:00 [entrez]
AID - 10.1203/00006450-200111000-00017 [doi]
PST - ppublish
SO  - Pediatr Res. 2001 Nov;50(5):633-40. doi: 10.1203/00006450-200111000-00017.