Cobra venom factor

CTL Cytotoxic T lymphocyte CTLA-4 Known to be co-expressed with CD20 on activated T cells CTMC Connective tissue mast cell CVF Cobra venom factor... 

Vogel, C.-W., and Muller-Eberhard, H.J. (1984) Cobra venom factor Improved method for purification and biochemical characterization./. Immunol. Meth. 73, 203. 

Opsonization by complement components also represents a potential barrier for intravenous gene delivery. Cationic charges of the particles activate the complement, which then takes part in particle elimination. This hurdle is possibly limited by using short hydrophobic chains, reducing the particle size, and eventually PEG insertion into lipoplexes (18). The interaction effect between the lipoplex and the complement might not be such a limitation. Indeed, it was reported that depletion of complement by injection of cobra venom factor and anti-C3 antibodies in mice indicated no differences upon intravenous injection of lipoplexes, neither in terms of tissue distribution nor in lipofection efficiency (19). 

Conjugations with iodoacetyl cross-linkers have been done using ricin and cobra venom factor (Myers et al., 1989 Vogel, 1987 Thorpe et al., 1984). The following generalized protocol for using SIAB is based on the method of Cumber et al. (1985). 

SMCC has been used to prepare immunotoxins with cobra venom factor (Vogel, 1987) and was compared to other cross-linkers in the preparation of gelonin and PAP conjugates (Lambert et al., 1985). 

Jatrorrhizine was found to possess anti-inflammatory activity as measured in the cobra venom factor-induced (CVF) rat paw edema. CVF edema was used to examine jatrorrhizine and other substances in order to detect novel compounds, since it has been shown that joint cyclooxygenase and lipoxygenase inhibitors, as well as immunoreactive drugs, exhibit more pronounced inhibitory effects on CVF in comparison to carrageenin-induced edema. CVF edema is dependent on activation of the complement system which plays an important role in acute and chronic inflammatory reactions, mediating the activity of immune complexes. This test system represents a functionally new type of acute inflammation via activation of the alternative complement pathway [290]. 

The requirement for two associated C3b molecules in the alternative pathway C5 convertase seems to restrict formation of this enzyme to the surface of particulate C activators where association of C3b may occur more readily. Even in the presence of stabilizing factors such as P, fluid-phase C5 convertase activity is very low. However, cobra venom factor, a C3b analogue (Alper and Balavitch, 1976), forms an efficient fluid-phase C5 convertase in association with factor B, perhaps because of the association or aggregation of the CoVF-Bb enzyme (Medicus, 1977). 

In vivo, RA has been reported to inhibit cobra venom factor (CVF)-induced paw edema, immune complex-mediated passive cutaneous anaphylaxis, and complement-dependent stimulation of prostacyclin synthesis. 

Rosmarinic acid (1) was first isolated from Rosmarinus officinalis L. (or Melissa officinalis L.) (Labiatae) [9]. It was found to act as a complement inhibitor, and several investigations were carried out to reveal its mode of action. Rosmarinic acid had effects on both the classical pathway C3-convertase and on the cobra venom factor-induced, alternative pathway convertase. It also exhibited inhibitory activity in a number of in vivo models in which complement activation plays a role Rosmarinic acid (0.316-3.16 mg/kg i.m.) reduced paw oedema induced by cobra venom... 

Although, as with human disease, complement deposition is not conspicuous in the vasculitic lesions, multiple experimental observations indicate that complement activation has an important pathogenic role in this model (64,65). Depletion of complement with Cobra venom factor completely prevents the development of glomerulonephritis and vasculitis after injection of MPO-IgG or transfer of anti-MPO splenocytes (64). Injection of anti-MPO IgG into mice with knockout of various complement genes demonstrates that the alternative complement pathway, but not the classic pathway or the lectin pathway, is required for anti-MPO IgG mediated disease induction (64). Specifically, C4-/- mice with blockade of the classic pathway and the lectin pathway develop disease that is same as in wild type mice, whereas C5-/-mice with blockade of all pathways and factor B -/- mice with selective blockade of the alternative pathway are completely protected from disease induction. In accord with an important role for complement, the CS-inhibiting monoclonal antibody (BB5.1) prevents the induction of glomerulonephritis in mice after injection of anti-MPO IgG and LPS (65). Even when the anti-C5 antibody is administered a day after the anti-MPO, there is a marked reduction in disease induction. 

Figure 8. The site of cobra venom factor (CVF) in complementary system.

Antibody-independent activation of the complement system starting with C3 can be achieved by means of CVF (cobra venom factor), which interacts with a serum cofactor. The CVF-serum cofactor complex acts on C3 and activates the terminal complement sequence (Fig. 8). The result may be cytolysis if bacteria or erythrocytes are involved, or the activation of a noncytolic mechanism such as the release of histamine from mast cells, platelets, or leukocytes, enhanced phagocytosis, contraction of smooth muscles, the aggregation and fusion of platelets, or the promotion of blood coagulation. 

B. Cobra Venom Factor (CVF). Because CVF activates an anti-complementary factor C3 without the presence of antibody, the injection of CVF to a person will activate the anticomplementary system and reduce the factors. This property is extensively used in organ transplantation. A person pretreated with CVF has a better chance of receiving an organ without rejection. 

STRUCTURE AND FUNCTION OF COBRA VENOM FACTOR, THE COMPLEMENT-ACTIVATING PROTEIN IN COBRA VENOM... 

Cobra Venom Factor (CVF) is an unusual venom component known to be present in the venom of the cobra species Naja, Ophiophagus, and Hemachatus of the Elapidae family (1). CVF is not a toxin in the classical sense. As a matter of fact, the purified molecule is not toxic. It specifically interacts with components of the serum complement system, leading to complement activation which in turn leads to the consumption of complement activity. 

Cobra venom factor is a glycoprotein with a molecular mass of 149,000 Da. It consists of three disulfide-linked chains with molecular masses of -- 68,500 Da (a-chain), --48,500 Da (P-chain), and -32,000 Da (y-chain) (Fig. 2). The y-chain shows size heterogeneity which is most likely due to differential processing at the C-terminus (5,6). From circular dichroism spectroscropy the secondary structure of CVF was determined to consist of 11% a-helix, 47% B-sheet, 18% P-tum, and 20% remainder (7). High resolution transmission electron microscropy revealed a somewhat irregular and elongated ellipsoid structure of the molecule with dimensions of 137 A by 82 A (7,8). 

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