Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo

G. L. Kukielka, C. W. Smith, G. J. LaRosa, A. M. Manning, L. H. Mendoza, T. J. Daly, B. J. Hughes, K. A. Youker, H. K. Hawkins, L. H. Michael, A. Rot, M. L. Entman

Research output: Contribution to journalArticle

196 Citations (Scopus)

Abstract

Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL- 8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.

Original languageEnglish (US)
Pages (from-to)89-103
Number of pages15
JournalJournal of Clinical Investigation
Volume95
Issue number1
StatePublished - 1995
Externally publishedYes

Fingerprint

Interleukin-8
Reperfusion
Myocardium
Ischemia
Genes
Canidae
Cardiac Myocytes
Messenger RNA
Neutrophils
Coronary Occlusion
Intercellular Adhesion Molecule-1
Recombinant Proteins
Veins
Complementary DNA
Staining and Labeling
Escherichia coli
Antibodies
Wounds and Injuries

Keywords

  • cell adhesion molecules
  • chemotaxis
  • myocardial infarction
  • myocardial reperfusion injury
  • neutrophils

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Kukielka, G. L., Smith, C. W., LaRosa, G. J., Manning, A. M., Mendoza, L. H., Daly, T. J., ... Entman, M. L. (1995). Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo. Journal of Clinical Investigation, 95(1), 89-103.

Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo. / Kukielka, G. L.; Smith, C. W.; LaRosa, G. J.; Manning, A. M.; Mendoza, L. H.; Daly, T. J.; Hughes, B. J.; Youker, K. A.; Hawkins, H. K.; Michael, L. H.; Rot, A.; Entman, M. L.

In: Journal of Clinical Investigation, Vol. 95, No. 1, 1995, p. 89-103.

Research output: Contribution to journalArticle

Kukielka, GL, Smith, CW, LaRosa, GJ, Manning, AM, Mendoza, LH, Daly, TJ, Hughes, BJ, Youker, KA, Hawkins, HK, Michael, LH, Rot, A & Entman, ML 1995, 'Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo', Journal of Clinical Investigation, vol. 95, no. 1, pp. 89-103.
Kukielka GL, Smith CW, LaRosa GJ, Manning AM, Mendoza LH, Daly TJ et al. Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo. Journal of Clinical Investigation. 1995;95(1):89-103.
Kukielka, G. L. ; Smith, C. W. ; LaRosa, G. J. ; Manning, A. M. ; Mendoza, L. H. ; Daly, T. J. ; Hughes, B. J. ; Youker, K. A. ; Hawkins, H. K. ; Michael, L. H. ; Rot, A. ; Entman, M. L. / Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo. In: Journal of Clinical Investigation. 1995 ; Vol. 95, No. 1. pp. 89-103.
@article{fdd52946178a49eca4a7204cb6570419,
title = "Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo",
abstract = "Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL- 8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.",
keywords = "cell adhesion molecules, chemotaxis, myocardial infarction, myocardial reperfusion injury, neutrophils",
author = "Kukielka, {G. L.} and Smith, {C. W.} and LaRosa, {G. J.} and Manning, {A. M.} and Mendoza, {L. H.} and Daly, {T. J.} and Hughes, {B. J.} and Youker, {K. A.} and Hawkins, {H. K.} and Michael, {L. H.} and A. Rot and Entman, {M. L.}",
year = "1995",
language = "English (US)",
volume = "95",
pages = "89--103",
journal = "Journal of Clinical Investigation",
issn = "0021-9738",
publisher = "The American Society for Clinical Investigation",
number = "1",

}

TY - JOUR

T1 - Interleukin-8 gene induction in the myocardium after ischemia and reperfusion in vivo

AU - Kukielka, G. L.

AU - Smith, C. W.

AU - LaRosa, G. J.

AU - Manning, A. M.

AU - Mendoza, L. H.

AU - Daly, T. J.

AU - Hughes, B. J.

AU - Youker, K. A.

AU - Hawkins, H. K.

AU - Michael, L. H.

AU - Rot, A.

AU - Entman, M. L.

PY - 1995

Y1 - 1995

N2 - Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL- 8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.

AB - Neutrophil adhesion and direct cytotoxicity for cardiac myocytes require chemotactic stimulation and are dependent upon CD18-ICAM-1 binding. To characterize the potential role of IL-8 in this interaction, canine IL-8 cDNA was cloned and the mature recombinant protein expressed in Escherichia coli BL21 cells. Recombinant canine IL-8 markedly increased adhesion of neutrophils to isolated canine cardiac myocytes. This adhesion resulted in direct cytotoxicity for cardiac myocytes. Both processes were specifically blocked by antibodies directed against CD18 and IL-8. In vivo, after 1 h of coronary occlusion, IL-8 mRNA was markedly and consistently induced in reperfused segments of myocardium. IL-8 mRNA was not induced in control (normally perfused) myocardial segments. Minimal amounts of IL-8 mRNA were detected after 3 or 4 h of ischemia without reperfusion. Highest levels of induction were evident in the most ischemic myocardial segments. IL-8 mRNA peaked in the first 3 h of reperfusion and persisted at high levels beyond 24 h. IL-8 staining was present in the inflammatory infiltrate near the border between necrotic and viable myocardium, as well as in small veins in the same area. These findings provide the first direct evidence for regulation of IL- 8 in ischemic and reperfused canine myocardium and support the hypothesis that IL-8 participates in neutrophil-mediated myocardial injury.

KW - cell adhesion molecules

KW - chemotaxis

KW - myocardial infarction

KW - myocardial reperfusion injury

KW - neutrophils

UR - http://www.scopus.com/inward/record.url?scp=0028798879&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028798879&partnerID=8YFLogxK

M3 - Article

C2 - 7814650

AN - SCOPUS:0028798879

VL - 95

SP - 89

EP - 103

JO - Journal of Clinical Investigation

JF - Journal of Clinical Investigation

SN - 0021-9738

IS - 1

ER -