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Lactoferrin: a promoter of polymorphonuclear leukocyte adhesiveness
Abstract:
Polymorphonuclear leukocytes (PMN) degranulate, adhere to vascular endothelium, or aggregate to each other following exposure of the cells to high concentrations of chemotactic stimuli such as formyl-methionyl-leucyl phenylalanine (FMLP). PMN released the specific granule product lactoferrin more readily in response to chemotactic stimuli, which correlated with promotion of PMN aggregation as measured by light transmission and enhanced PMN adherence. Both concanavalin A (Con-A) and phorbol myristate acetate (PMA), agents that lead to specific granule discharge, induced and sustained human PMN aggregation. Similarly, supernatants, generated from Con-A-treated PMN, aggregated fresh PMN in the presence of alpha-methylmannoside, a competitive inhibitor of the lectin. Anti-human lactoferrin IgG but not normal goat IgG blunted the aggregation elicited by both PMA and FMLP. Both human milk lactoferrin and rabbit PMN lactoferrin aggregated human lactoferrin promoted PMN adherence to endothelial cells. The enhanced PMN stickiness was correlated with the early phase of degranulation. Thus, PMN lactoferrin serves an autoregulatory role to retain PMN at inflammatory sites to amplify the inflammatory response.
Insights
Polymorphonuclear leukocytes (PMN) use lactoferrin to stick to blood vessels and clump together. This process, triggered by inflammatory signals, helps keep immune cells at infection sites to enhance the body's response.
Area of Science:
- Immunology
- Cell Biology
- Biochemistry
Background:
- Polymorphonuclear leukocytes (PMNs) are crucial immune cells involved in inflammatory responses.
- PMN activation leads to degranulation, adhesion to endothelium, and aggregation.
- Chemotactic stimuli, like formyl-methionyl-leucyl phenylalanine (FMLP), trigger these PMN responses.
Purpose of the Study:
- To investigate the role of lactoferrin in PMN activation and inflammatory processes.
- To determine if lactoferrin mediates PMN aggregation and adherence to endothelial cells.
- To elucidate the autoregulatory function of PMN-derived lactoferrin in inflammation.
Main Methods:
- Stimulation of human PMNs with chemotactic agents (FMLP, PMA) and Concanavalin A (Con-A).
- Measurement of PMN aggregation using light transmission.
- Assessment of PMN adherence to endothelial cells.
- Inhibition studies using anti-human lactoferrin IgG and alpha-methylmannoside.
Main Results:
- Lactoferrin release from PMNs correlated with increased PMN aggregation and adherence.
- Con-A and PMA induced and sustained PMN aggregation.
- Supernatants from Con-A-treated PMNs aggregated fresh PMNs.
- Anti-lactoferrin IgG significantly reduced PMA- and FMLP-induced PMN aggregation.
- Lactoferrin promoted PMN adherence to endothelial cells, linked to early degranulation.
Conclusions:
- PMN-derived lactoferrin plays a key role in promoting PMN aggregation and adherence.
- Lactoferrin acts as an autocrine factor, retaining PMNs at inflammatory sites.
- This mechanism amplifies the inflammatory response by concentrating immune cells at sites of injury or infection.