The purple acid phosphatases and uteroferrin belong to a diverse multifunctional class of binuclear ironcontaining proteins that includes haemerythrin and ribonucleotide reductase. In the pig, uteroferrin has been implicated in the delivery of iron to the foetus, but the role of the related human type 5 acid phosphatase that is principally found in resident tissue macrophages is not yet clear. To define further the function of this metalloenzyme, we have isolated and sequenced a cDNA clone for type 5 acid phosphatase and investigated expression of its gene in human tissues. The phosphatase clone contains an open reading frame of 975 bp and encodes a protein of 325 amino acids, including a signal peptide of 19 residues and two potential sites for N-glycosylation. The type 5 acid phosphatase gene mapped to the short arm of human chromosome 19 and was found to have a restriction fragment length polymorphism on digestion with XbaI.Expression of phosphatase mRNA was restricted to mononuclear phagocytes and the enzyme was induced > 20-fold on transformation of normal human monocytes to macrophages by culture in serum-supplemented medium. Type 5 acid phosphatase thus represents a tightly regulated system for the study of molecular events in the differentiation programme of the normal macrophage.Type 5, tartrate-resistant, purple acid phosphatase is a basic, iron-binding protein with high activity towards phosphoproteins, ATP, and 4-nitrophenyl phosphate but with little action on aliphatic phosphates [I, 21. The isoenzyme is found in human alveolar macrophages [3] and osteoclasts [4] and is pathologically increased in Gaucher's cells [5] and in the hairy cells of leukaemic reticuloendotheliosis [6], now known as hairy cell leukaemia. It is thus expressed principally in cells of the human mononuclear macrophage system.Recently the protein has been purified from human and bovine spleen, where it is associated with a particulate fraction [7, 81. lmmunochemical and enzymatic studies [9, 101 as well as protein sequence analysis [I 11 have shown that the splenic enzyme is homologous to uteroferrin, a purple iron-binding protein abundant in the uterine secretions of pregnant sows. Physiological studies in vivo have implicated uteroferrin in the delivery of maternal iron to the developing piglet [12, 131 but the possibility of a similar function for the human tartrateresistant acid phosphatase has not been investigated. However, ultrastructural studies [14] indicate association of the bovine protein with ferritin and haemosiderin aggregates in splenic macrophages, suggesting that it may participate in the Correspondence to

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The unknown allele that predisposes to the development of haemochromatosis in man has been localized to the HLA class I region on the short arm of chromosome 6. We have utilized pulsed-field gel electrophoresis in conjunction with probes that map within, or in the vicinity of, this region to search for structural lesions that may further define the disease locus. Using the enzyme Mlu I, fragments that associated specifically with the HLA-A23, A31 and B8 alleles were identified. However, in members of three pedigrees affected by haemochromatosis, and in six unrelated patients with the disorder, no disease-specific differences were detected in the DNA fragments with four restriction enzymes and eight probes when compared with healthy individuals. These data suggest that the lesion responsible for hereditary haemochromatosis lies beyond the resolution of this technique and does not involve large structural deletions or extensive re-arrangements in this highly polymorphic region of the genome.

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