Chemotactic Factors

Definition
Chemotactic factors are substances that stimulate cellular locomotion/migration1. Some examples include formyl peptides, chemokines and complement proteins-3a and 5a1.

Discovery
Chemotaxis and chemotactic factors were described as early as 1880’s. The whole process of chemotaxis by chemotactic factors was understood in E.coli in 19742.

Classification
Chemotactic factors are of several groups:
1)Chemokines- b-Thromboglobulin, Chemokines C, CC , CX3C and CXC , Macrophage Inflammatory Proteins
2)Chemotactic Factors, Eosinophil-N-Formylmethionine Leucyl-Phenylalanine
3)Leukocyte Migration-Inhibitory Factors
4)Macrophage Migration-Inhibitory Factors-N-Formylmethionine Leucyl-Phenylalanine
5)Complement proteins- 3a and 5a3.

Structural Characteristics
Structural characteristics of some chemotactic factors are highlighted below:
1)Chemokines have a characteristic composition of beta-sheets and an alpha helix provides expression of sequences required for interaction with the chemokine receptors4.
2)Complement protein C3a is a 77 amino acid peptide with a random coiled C-terminus and a well defined helical N terminus5.
3)Formylated peptides have acylated N-terminal amino group and a strongly hydrophobic C- terminal amino acids6.

Mode of action
In prokaryotic cells, chemical gradients are sensed through multiple transmembrane receptors, called methyl accepting chemotaxis proteins (MCPs), which vary in the molecules that they detect7. These receptors may bind attractants or repellents directly or indirectly through interaction with proteins of periplasmatic space7. The signals from these receptors are transmitted across the plasma membrane into the cytosol, where Che proteins are activated. The Che proteins alter the tumbling frequency, and alter the receptors7.

Eukaryotic cells sense the presence of chemotactic stimuli through the use of 7-transmembrane heterotrimeric G-protein coupled receptors that in turn elicit downstream signaling pathways that ultimately lead to cell migration.7

Functions
Chemoattractants indicate the presence of food to bacteria or if they are repellents they indicate the presence of noxious substances1. Chemoattractants are part of immune system where they attract neutrophils and macrophages to the site of inflammation8. They also function in nervous system where they can guide spinal commissural axons9. Chemokines generated from lymphatic endothelial cells and lymph node cells play a role in the directional migration of dendritic into lymph nodes10. Chemoattractants are also implicated in autoimmune disorders11.

References
1.Kohidai L and Csaba G (1988). Chemotaxis and chemotactic selection induced with cytokines (IL-8, RANTES and TNF alpha) in the unicellular Tetrahymena pyriformis. Cytokine 10, 481–6.
2.Adler J and Tso WW (1974). Decision-making in Bacteria: Chemotactic response of Escherichia Coli to conflicting stimuli. Science 184: 1292–4
3.Book: Chemotaxis, by Eisenbach M, Lengele JW. 253-270.
4.Fernandez E, Lolis E (2002). Structure, function, and inhibition of chemokines. Annu Rev Pharmacol Toxicol., 42, 469–99.
5.Nettesheim DG, Edalji RP, Mollison KW, Greer J, and Zuiderweg ER (1988). Secondary structure of complement component C3a anaphylatoxin in solution as determined by NMR spectroscopy: differences between crystal and solution conformations. Proc Natl Acad Sci U S A; 85(14): 5036–5040.
6.Book: Biology of the chemotactic response by J. M. Lackie, Peter Charles Wilkinson, 56-58.
7.Devalaraja MN and Richmond A. Multiple chemotactic factors: fine control or redundancy? Trends in Pharmacological Sciences, 20 (4), 151-156.
8.Haribabu B, Richardson RM, Verghese MW, Barr AJ, Zhelev DV and Snyderma R (2000). Function and regulation of chemoattractant receptors. Immunologic response, 22, 271-279.
9.Galko MJ, Tessier-Lavigne M (2000). Function of an axonal chemoattractant modulated by metalloprotease activity. Science, 289(5483), 1365-7.
10.Wang B, Amerio P, and Sauder DN (1999). Role of cytokines in epidermal Langerhans cell migration. Journal of Leukocyte Biology, 66, 33-39.
11.Tesch GH, Maifert S, Schwarting A, Rollins BJ, Kelley VR (1999). Monocyte chemoattractant protein 1-dependent leukocytic infiltrates are responsible for autoimmune disease in MRL-Fas(lpr) mice. J Exp Med, 190(12), 1813-24.