Dennis E. Chenoweth

Biocompatibility of artificial organs: an overview

Papers that are presented in this symposium on biocompatibility of foreign surfaces used in artificial organs are commented upon and set in an overall context of the biocompatibility of foreign surfaces to blood. A working formulation of the events comprising lack of biocompatibility of hemodialysis membranes to the complement system is given as a possible model to which other foreign surfaces may be compared.

Choosing a membrane.

Fifteenth Annual Meeting, Am Soc Nephrol, 1982, 71A 39. Cheung A, LeWinter M, Chenoweth DE, et al: Un- published observations, 1982 40. Baldamus CA, Ernst W, Fassbinder W, et al: Differing hemodynamic stability due to differing sympathetic response: Comparison of ultrafiltration hemodialysis and hemofiltration. Proc Eur Dial Transplant Assoc 17:205-210, 1980 41. Hampl H, Paeprer H, Unger V, et al: Hemodynamic during hemodialysis, sequential ultrafiltration and hemofiltra- tion . 1 Dial 3:51-71 , 1979 42. Bergstrom 1, Asaba H, Furst P, et al : Dialysis ultrafiltra- tion and blood pressure . Proc Eur Dial Transplant Assoc 13:293-305, 1976 43. Mrava GL, Weber DC, Malchesky PS, et al: Computer- ized data analysis of hemodialyzers by a standard protocol shows true effective membrane area. Trans Am Soc Artif In- tern Organs 16: 155-163, 1970 44. Colton CK, Henderson LW, Ford CA, et al: Kinetics of hemodiafiltration. I. in vitro transport characteristics of a hol- low fiber blood ultrafilter. 1 Lab Clin Med 85 :355-371, 1975 45 . Henderson LW, Colton CK, Ford CA: Kinetics ofhemo- diafiltration. n. Clinical characterization of a new blood cleansing modality. 1 Lab Clin Med 85:372-391 , 1975 46. Leypoldt lK, Frigon RP, Henderson LW: Dextran siev- ing coefficients of hemofiltration membranes. Trans Am Soc Artif Inter Organs (in press) 47. Shaldon SH, Silva H, Rosen M: Technique for refrigerated coil preservation hemodialysis with femoral venous cathe- terization. Br Med J 2:411-413, 1964 48. Deane N, Bemus lA: Multiple use of hemodialyzers. Final Report, National Institute of Arthritis, Diabetes and Di- gestive and Kidney Diseases, 1981, pp 1254 49. Shaldon S, Chevallet M, Maraouri M, et al: Dialysis associated autoantibodies. Proc Eur Dial Transplant Assoc 13 :339-346, 1976 50. Hoenich NA: Personal communication 51. Shaldon S: Progress from haemodialysis. Nephron 27:26, 1981 52. Henderson LW: Comparison of hemodialysis and hemo-

Complement Mediators of Inflammation

Publisher Summary This chapter discusses the chemistry and biology of three complement-derived polypeptides, termed anaphylatoxins, that function most importantly as mediators of inflammation. The human anaphylatoxins C3a, C4a, and C5a are biologically active low molecular weight fragments derived from the complement components C3, C4, and C5, respectively. All of these polypeptides share a common biological activity termed as spasmogenicity; that is, they promote smooth muscle contraction and induce increased vascular permeability. It is these biological properties that account for the ability of these molecules, and C5a in particular, to induce an anaphylactic response in appropriate test animals—thus their designation as anaphylatoxins. Once the anaphylatoxins are formed in human serum, their spasmogenie activities are rapidly abrogated by an enzyme that acts as an anaphylatoxin inactivator. This exopeptidase, serum carboxypeptidase N, removes the COOH-terminal arginyl residue from each of the anaphylatoxin molecules and converts them to their des-Arg derivatives. All three of the human anaphylatoxins display spasmogenic activity. In the case of C3a and C4a, this activity is rapidly destroyed by a serum exopeptidase that selectively removes their COOH-terminal arginyl residues. Normally, this enzymatic control mechanism is so effective that biologically active forms of these molecules are not found circulating in blood. As a result, the biological properties of these two anaphylatoxins may only be manifest at local sites in vivo .

Regulation of Neutrophil Migratory Function in Burn Injury by Complement Activation Products

Polymorphonuclear neutrophils were isolated from patients with burn injury and random mobility, chemotaxis in response to C5adesArg (as agarose-activated control serum) and to N-formyl-methionyl-leucyl-phenylalanine (F-Met-Leu-Phe) were assessed. For a group of eight patients identified as not experiencing systemic infection, all three neutrophil migratory functions were observed to fall below control levels, beginning 4 to 6 days following burn injury, and to return to control levels after 21 to 30 days of hospitalization. Over this time the chemotactic differential (distance chemotactic migration-distance random migration) for F-Met-Leu-Phe remained positive, while the chemotactic differential for activated serum became nil after postburn day 4. This temporal, specific loss of a chemotactic response to activated serum was associated with rises in immunoreactive plasma C3a and C5a. This pattern of loss of chemotactic function was associated with a selective loss of C5a but not F-Met-Leu-Phe binding activity. These results demonstrate that burn injury can alter neutrophil migratory functions generally, and specifically depress chemotactic responsiveness to activated serum. The mechanism of the latter phenomenon appears to be related to desensitization of circulating neutrophils to C5a due to complement activation.