Bacteria‐induced protein P4 (hemolin) from Manduca sexta: A member of the immunoglobulin superfamily which can inhibit hemocyte aggregation

Abstract

The synthesis of a number of hemolymph proteins is induced in insects in response to bacterial infections. The major induced hemolymph protein in larvae of Manduca sexta is a glycoprotein of Mr = 48,000 known as P4. We have isolated a clone for P4 from a fat body cDNA library constructed from RNA isolated from larvae injected with bacteria. The cDNA has an open reading frame encoding a 411 residue polypeptide with a hydrophobic NH2-terminal sequence, which appears to be a signal peptide. Analysis of the deduced amino acid sequence shows that P4 is a member of the immunoglobulin (Ig) gene superfamily, and is composed largely of four C2 type Ig domains. The M. sexta P4 amino acid sequence is 60% identical with hemolin (P4) from Hyalophora cecropia. The name "hemolin" has also been adopted for the M. sexta P4 protein. Hemolin mRNA levels in fat body begin to increase within 1 h after injection of bacteria into fifth instar larvae and within 4 h after injection of adults. Hemolin associates with the surface of hemocytes and inhibits hemocyte aggregation responses, suggesting a role for the protein in modulating hemocyte adhesion during recognition and response to bacterial infections in insects.

Reconfiguration of the immune system network during food limitation in the caterpillarManduca sexta

“…This may be an important alternative method of reducing pathogen-generated damage if molecules such as GSH are unavailable. Hemolin is a much larger molecule than GSH (it contains 411 amino acids, including several that contain sulphur; Ladendorff and Kanost, 1991), but it may be less likely to dampen early immune responses than GSH. The changes in hemolin and GSH may reflect network changes designed to both enhance PO activity and to mitigate some of the costs due to damage.…”

Losac, the First Hemolin that Exhibits Procogulant Activity through Selective Factor X Proteolytic Activation

“…Hemolin is a bacteria-inducible immunoglobulinlike protein whose role in insect immunity has been better studied. In the last 2 decades, independent studies have demonstrated that hemolin proteins are multifunctional molecules involved in a diverse range of cell interaction and are able to (a) bind lipopolysaccharides and be up-regulated in hemolymph during infections (15)(16)(17); (b) be up-regulated during metamorphosis (18,19); (c) promote opsonin-like effects, such as increased cell adhesion and phagocytosis (20,21); (d) agglutinate bacterial cells (17,22); (e) bind to hemocytes and inhibit their aggregation (15,20,22,23); and (f) regulate embryonic development (24,25).…”

Is the distinction between innate and adaptive immunity in invertebrates still as clear-cut as thought?

“…This molecule belongs to the IgSF and seems to be involved in the immune recognition process (Andersson & Stainer 1987;Sun et al 1990;Ladendorff et al 1991;Schmidt et al 1993). A homologue of human Down syndrome cell adhesion molecule (DSCAM) belonging to IgSF has been found in Drosophila.…”