Enhancement of hexose uptake in human polymorphonuclear leukocytes by activated complement component C5a

Area of Science:

• Immunology
• Cellular Biology
• Biochemistry

Background:

• Polymorphonuclear leukocytes (PMNLs) rely on glucose for essential functions like motility and phagocytosis.
• The complement system, particularly C5a, plays a role in immune responses and cellular functions.

Purpose of the Study:

• To investigate the effect of complement component C5a on glucose transport in human PMNLs.
• To determine the mechanism by which C5a influences glucose uptake and its potential as a biomarker for complement activation.

Main Methods:

• Human PMNLs were incubated with zymosan-activated serum or purified C5a.
• Uptake of 2-deoxy-D-[3H]glucose was measured to assess carbohydrate transport.
• Kinetic analysis (K(m) and V(max)) was performed to characterize the transport mechanism.
• C5a's effect was compared to insulin and tested on other cell types.

Main Results:

• C5a significantly increased deoxyglucose transport into PMNLs in a concentration-dependent manner (>700% increase).
• C5a decreased the K(m) for deoxyglucose transport from 0.53 to 0.11 mM, indicating enhanced carrier affinity, without altering V(max).
• This enhanced transport was specific to PMNLs and not observed in erythrocytes, platelets, or lymphocytes, and was not mediated by increased hexokinase activity or insulin.

Conclusions:

• Complement component C5a enhances glucose uptake in PMNLs by stimulating carrier-mediated transport, not by altering V(max) or hexokinase activity.
• The optimal concentration for C5a-induced glucose transport aligns with that for PMNL chemotaxis.
• PMNL glucose uptake serves as a highly sensitive indicator for the activation of the fifth component of complement (C5).