Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation

Eric B. Lynam, Scott I. Simon, Yvan P. Rochon, Larry A. Sklar

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L- selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.

Original languageEnglish (US)
Pages (from-to)3303-3311
Number of pages9
JournalBlood
Volume83
Issue number11
StatePublished - Jun 1 1994
Externally publishedYes

Fingerprint

L-Selectin
Lipopolysaccharides
Neutrophils
Agglomeration
Adhesives
Peptides
Immunoglobulin Fab Fragments
Latex
Microspheres
Endotoxins
Integrins
Blood Proteins
Carrier Proteins
Membrane Proteins
Blood
Up-Regulation
Monoclonal Antibodies
Ligands
Molecules

ASJC Scopus subject areas

  • Hematology

Cite this

Lynam, E. B., Simon, S. I., Rochon, Y. P., & Sklar, L. A. (1994). Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. Blood, 83(11), 3303-3311.

Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. / Lynam, Eric B.; Simon, Scott I.; Rochon, Yvan P.; Sklar, Larry A.

In: Blood, Vol. 83, No. 11, 01.06.1994, p. 3303-3311.

Research output: Contribution to journalArticle

Lynam, EB, Simon, SI, Rochon, YP & Sklar, LA 1994, 'Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation', Blood, vol. 83, no. 11, pp. 3303-3311.
Lynam EB, Simon SI, Rochon YP, Sklar LA. Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. Blood. 1994 Jun 1;83(11):3303-3311.
Lynam, Eric B. ; Simon, Scott I. ; Rochon, Yvan P. ; Sklar, Larry A. / Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation. In: Blood. 1994 ; Vol. 83, No. 11. pp. 3303-3311.
@article{8a525f0fc19342d18a057dc317a9920c,
title = "Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation",
abstract = "Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L- selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.",
author = "Lynam, {Eric B.} and Simon, {Scott I.} and Rochon, {Yvan P.} and Sklar, {Larry A.}",
year = "1994",
month = "6",
day = "1",
language = "English (US)",
volume = "83",
pages = "3303--3311",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "11",

}

TY - JOUR

T1 - Lipopolysaccharide enhances CD11b/CD18 function but inhibits neutrophil aggregation

AU - Lynam, Eric B.

AU - Simon, Scott I.

AU - Rochon, Yvan P.

AU - Sklar, Larry A.

PY - 1994/6/1

Y1 - 1994/6/1

N2 - Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L- selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.

AB - Human neutrophils are primed in the presence of complexes of lipopolysaccharide (LPS) with its serum binding protein (LBP) in a manner dependent on CD14. Cellular consequences of priming include increased responsiveness, the upregulation of surface proteins including the adhesive integrin CD11b/CD18 (Mac-1), the increased binding of certain ligands to CD11b/CD18, and the concurrent shedding of the L-selectin homing receptor. Because expression of both CD11b/CD18 and L-selectin is obligatory for formyl peptide-stimulated neutrophil aggregation in vitro (Simon et al, Blood 82:1097, 1993), we have examined the consequences of bacterial endotoxin on the expression of neutrophil adhesive molecules. We observed that the exposure of neutrophils to LPS/LBP, while enhancing the surface numbers and adhesive function of CD11b/CD18 for latex particles, did not induce aggregation. In contrast, as the LPS/LBP concentration increased (ED50 = 30 ng/mL LPS/LBP), the ability of neutrophils to aggregate decreased in parallel with the shedding of L-selectin. Moreover, when L-selectin adhesive activity was blocked by treatment with Fab fragments of Dreg-200, aggregation was inhibited to an extent roughly proportional to the available L-selection. Blocking of LPS/LBP with CD14-specific monoclonal antibodies suppressed L- selectin shedding and preserved formyl peptide-stimulated aggregation. Taken together, the data suggest that inhibition of neutrophil aggregation by LPS/LBP is related to the expression of L-selectin via CD14 rather than LPS inhibition of CD11b/CD18 function during cellular stimulation.

UR - http://www.scopus.com/inward/record.url?scp=0028364707&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028364707&partnerID=8YFLogxK

M3 - Article

C2 - 7514906

AN - SCOPUS:0028364707

VL - 83

SP - 3303

EP - 3311

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11

ER -