Reperfusion of the previously ischémie myocardium is attended by an intense acute inflammatory reaction that has been linked to myocardial injury. A major feature of this reaction is neutrophil (PMN) infiltration of the viable border zone abutting the infarct and we have shown, in vitro, that PMN injure cardiac myocytes by a mechanism involving Mac-1 adhesion to myocyte ICAM-1. Since PMN activation is associated with prolonged viability, we have examined the cellular changes which occur in PMN that have transmigrated from venu l es and infiltrated the tissue. PMN in the venules and in the peri venu I ar sheath strongly stain for Mac-1 at all time periods. However, PMN that have infiltrated into the tissue begin losing Mac-1 by one hour and by five hours of reperfusion virtually all of the neutrophils have lost their Mac-1. Migration into tissues can be associated with phenotypic changes, as exemplified by the monocytemacrophage. We postulated mat neutrophils undergo a similar change. In situ hybridization and immunostaining demonstrated that, at one and three hours of reperfusion, 1L-6 mRNA and protein expression occurred only in mononuclear cells. However, at five hours, a large proportion of the neutrophils (specifically identified by Mab SG8H6) were likewise stained for IL-6 mRNA and for IL-6 protein. We propose that the tissue PMN undergoes a transition and exists in vivo with a divergent phenotype from the traditional circulating PMN. In absence of Mac-1, this transformed PMN may no longer injure cells but may assume a secretory phenotype involved in healing.
|Original language||English (US)|
|Journal||Journal of Investigative Medicine|
|State||Published - Jan 1 1996|
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology(all)