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Abnormal stimulated adherence of neonatal granulocytes: impaired induction
of surface Mac-1 by chemotactic factors or secretagogues
DC Anderson, KL Freeman, B Heerdt, BJ Hughes, RM Jack and CW Smith
To identify possible secretory determinants of impaired hyperadherence and
stimulated migration of neonatal granulocytes (NGs), we performed
correlative studies of: (a) specific granule content and exocytosis, (b)
secretago-gue-mediated upregulation of f-met-leu-phe (fMLP) receptors, (c)
the chemotactic induction of the adhesive glycoproteins Mac-1 alpha
(complement receptor 3) and beta, and (d) morphometric assessments of
specific (peroxidase negative) granule depletion following chemotactic
stimulation. Lactoferrin (LF) content of NG suspensions (cord blood or
peripheral blood cells) was profoundly diminished (mean +/- SD 51% +/- 18%
of normal) as compared with healthy adult granulocytes (AGs). Despite
diminished cellular content, LF release by NG suspensions in response to
fMLP was comparable to that of AGs. In contrast, LF release by NG
suspensions was significantly diminished in response to phorbol myristate
acetate (PMA) or calcium ionophor A23187 and/or during stimulated cell
spreading, experimental conditions promoting overall greater LF depletion
than chemotactic stimuli. In addition, NGs demonstrated an impaired
capacity to upregulate fMLP receptors in response to PMA or A23187 when
tested under the same experimental conditions. Baseline expression of the
adhesive glycoproteins Mac-1 alpha and beta on NG surfaces was normal, but
induction or upregulation of these proteins by chemotactic concentrations
of fMLP, C5a as well as secretory (high) concentrations of PMA and A23187,
was significantly diminished as compared with AGs. In contrast, chemotactic
induction of the surface expression of the complement receptor-1 (CR-1) on
NGs was normal. An impaired induction of Mac-1 alpha or beta was directly
related to an impaired enhancement of adherence of NG in response to fMLP
over a chemotactically relevant concentration range (10(-10) to 10(-7)
mol/L). Moreover, in blocking- incubation experiments using anti-Mac-1
alpha/beta monoclonal antibodies (MAbs), significantly less inhibition of
adherence by these MAbs was evident with fMLP-stimulated NG as compared
with AG suspensions. Under selected chemotactic conditions, ultrastructural
assessments of NGs demonstrated diminished peroxidase-negative granule loss
in association with diminished granule-membrane fusion and the "addition"
of plasma membrane. These studies suggest that abnormal expression of
multiple surface determinants derived from peroxidase- negative granules or
other intracellular pools may contribute to deficient chemotaxis or other
inflammatory functions of NGs.(ABSTRACT TRUNCATED AT 400 WORDS)
Volume 70,
Issue 3,
pp. 740-750,
09/01/1987
Copyright © 1987 by The American Society of Hematology
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