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Monocyte activation after burns and endotoxemia
Abstract:
We describe the settings in which monocytes (M) are activated, as monokines may mediate organ dysfunction occurring after surgery and sepsis. To monitor M activation, we measured the relative number of M cell surface receptors for C3b and iC3b by indirect immunofluorescence. M exposed to increasing concentrations of endotoxic lipopolysaccharide (LPS) expressed increased mean cell surface C3b receptor-dependent fluorescence (35 buffer alone vs 354 LPS at 1000 ng/ml) and iC3b receptor-dependent fluorescence (78 vs 404). To determine whether this M activation could be reproduced by endotoxemia, normal volunteers were randomly administered saline or a single dose of LPS (20 u/kg). We found increased M cell surface C3b receptors 4 hr after LPS (341 LPS (n = 22) vs 168 saline (n = 20)) which returned to control levels at 24 hr. A similar transient increase was seen at 4 hr with M cell surface iC3b receptors (304 LPS (n = 23) vs 104 saline (n = 20)). To determine whether this could be used clinically, seven patients with burns (10-70% body surface area) were serially sampled up to 50 days. Each patient demonstrated elevations of M cell surface C3b and iC3b receptors, which gradually decreased over many weeks. For the group as whole, mean M cell surface C3b receptor-dependent fluorescence was 287, Days 0-5 postburn (vs 132 in 147 normals); 315, Days 6-9; 217, Days 10-13; 237, Days 14-19; and 185, Days 20+.(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Monocyte (M) activation, indicated by increased C3b and iC3b receptors, occurs after endotoxin exposure and in burn patients. This suggests a potential clinical marker for inflammatory responses and organ dysfunction following surgery or sepsis.
Area of Science:
- Immunology
- Cell Biology
Background:
- Monocytes (M) play a crucial role in immune responses.
- Monokine release from activated monocytes can contribute to organ dysfunction after surgery and sepsis.
Purpose of the Study:
- To investigate monocyte (M) activation by measuring cell surface receptors for C3b and iC3b.
- To assess if M activation correlates with clinical conditions like endotoxemia and burn injuries.
Main Methods:
- Monocyte (M) activation was assessed using indirect immunofluorescence to quantify cell surface receptors for C3b and iC3b.
- Experiments involved exposing monocytes to varying concentrations of lipopolysaccharide (LPS) in vitro.
- Human volunteers received LPS or saline, and burn patients were serially sampled.
Main Results:
- In vitro LPS exposure increased M C3b and iC3b receptor expression.
- In vivo LPS administration to volunteers caused transient increases in M C3b and iC3b receptors.
- Burn patients exhibited elevated M C3b and iC3b receptors for extended periods post-injury.
Conclusions:
- Monocyte (M) activation, marked by increased C3b and iC3b receptors, is induced by endotoxin.
- Elevated M C3b and iC3b receptors in burn patients suggest a prolonged inflammatory state.
- This M activation marker may have clinical utility in monitoring inflammatory conditions and organ dysfunction.