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Relationship between Molecular Size and Intra- and Extravascular Distribution of Protein Antigens¹

Department of Experimental Pathology, Scripps Clinic and Research Foundation, LaJolla, California

Abstract

Plasma proteins varying in molecular weight from 50,000 to 950,000 were radiolabeled and injected into rabbits and the lymph to plasma concentration ratios (C_L/C_P) of the various proteins were measured 3 days following injection. The amount of protein in the extravascular fluid spaces after equilibration, as measured by the C_L/C_P, correlated exponentially with the effective hydrodynamic diffusion radius of the protein. An exponential relationship also was observed between C_L/C_P and molecular weight for globular proteins, whereas fibrinogen, which is a spindle-shaped protein, showed only a correlation with the effective hydrodynamic diffusion radius and not with the molecular weight. No correlation between the intra- and extravascular distribution and half-lives of the various homologous and heterologous proteins was observed. The immunoglobulins of similar molecular size, but different chemical structure, as human A-monomer, human G and rabbit G, showed a similar lymph to plasma concentration ratio following equilibration.

Following intravenous injection, a larger percentage of bovine serum albumin (BSA) complexed with Fab fragments from purified anti-BSA remained in the intravascular fluid spaces than of BSA alone after complete equilibration.

Similar to the C_L/C_P, the calculated extravascular lymph space occupied by the various proteins correlated exponentially with the effective hydrodynamic diffusion radius of the protein.

The importance of the in vivo distribution and the behavior of protein antigens in relation to immunologic phenomena is discussed. With a given blood concentration, the concentration of serum protein antigens in the extravascular fluid space varies considerably with antigens of different molecular sizes.

Footnotes

This is publication number 237 from the Department of Experimental Pathology, Scripps Clinic and Research Foundation, LaJolla, California. The work was supported by United States Public Health Service Grant AI 07007-02 and Atomic Energy Commission Contract AT (04-3)-410.

² Supported by a fellowship from the Arthritis Foundation.

³ Faculty Research Associate of the American Cancer Society (PRA-38).

⁴ Supported by United States Public Health Service Research Career Award (5-K6-GM-6936).

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